Oncology

Oncology: timeline of key events

Fibiger published the first randomisation method for a clinical trial. The aim of the trial, conducted in 1898, was to investigate the effect of serum therapy on diphtheria. Fibiger would later go on to win the 1926 Nobel Prize for Medicine for demonstrating a roundworm could cause stomach cancer in rats and mice. Following his death researchers showed that the roundworm could not cause cancer and were due to vitamin deficiency and that Fibiger had mistakenly confused non-cancerous tumours for cancerous tumours in his experiments. 1867-04-23T00:00:00+0000A pathologist, Rous won the 1966 Nobel Prize for showing how viruses could cause cancer. He demonstrated this in 1910 by transplanting some material from a cancer tumour taken from a chicken into a healthy chicken. The healthy chicken developed cancer. Other scientists struggled to replicate his experiment in mammals so his discovery was initially dismissed. 1879-10-05T00:00:00+0000Based on the observation that some tumours shrink in patients with a bacterial skin infection, the surgeon William Coley treated a 21 year old man with inoperable sarcoma with mixture containing heat-treated bacteria. The man went into complete remision. W. Coley, 'The Treatment of Malignant Tumors By Repeated Inoculations of Erysipelas: With A Report of Ten Original Cases', The American Journal of Medical Sciences, 105 (1893): 487-511. 1893-05-01T00:00:00+0000Antiserum preparted against human oesteogenic sarcoma in an ass and 2 dogs. Reported successful in treating 50 patients suffering from cancer of the stomach and chest wall. J Hericourt, C Richet, 'Traitement d'un cas de sarcome par la sarcome par la serotherapie', Seances Acad Sci, 120 (1895), 948-50.1895-01-01T00:00:00+0000The vaccine was developed by William Coley, a New York surgeon, together with the pharmaceutical company Parke, Davis & Co. The vaccine contained a combination of heat-killed bacteria. 1899-01-01T00:00:00+0000The work was carried out independently by Leo Loeb, in Canada and the US, and by Carl Jensen in Copenhagen. Results from the experiments showed some animals were more susceptible to transplanted tumour tissue than others. This ignited a debate 1901-01-01T00:00:00+0000Huggins was a surgeon and medical researcher who shared the 1966 Nobel Prize for showing the relationship between certain hormones and certain cancers. In 1941 he demonstrated that it was possible to slow down the growth of prostrate cancer using oestrogen, a female hormone. This is now a common method for treating prostrate cancer. Later on Huggins demonstrated that it was possible to slow down some breast cancers by removing the ovaries and adrenal glands which produce oestrogen. Drugs to block the body's production of oestrogen are now routinely used for treating breast cancer. 1901-09-22T00:00:00+0000Patients reported an alleviation of their symptoms. E von Leyden, F Blumenthal, 'Vorlaufige Mittheilungen uber einige Ergebnisse der Krebsforschung aug der I. medizinischen Klinik', Deutsche Med Wschr, 28 (1902), 637-8.1902-01-01T00:00:00+0000E. Freund, G. Kaminer, 'Ueber die Beziehungen zwischen Tumorzellen und Blutserum', Biochem. Ztschr, 26 (1910) 26, 312-24.1910-01-01T00:00:00+0000The research was carried out by Peyton Rous. The idea that a virus could cause cancer was greeted with scepticism in the scientific community.1911-01-01T00:00:00+0000 JB Murphy, 'Studies on tissue specificity', Journal of Experimental Medicine, 19 (1914), 181-86.1914-01-01T00:00:00+0000Dulbecco shared the 1975 Nobel Prize for Medicine for 'discoveries concerning the interaction between tumour viruses and the genetic material of the cell.' His work not only aided better understanding of how viruses cause cancer but also HIV. 1914-02-22T00:00:00+0000The experiments involved increasing the number of lymphocytes in the blood of mice by treating them with low doses of X-rays. JB Murphy, JJ Morton, 'The effects of X-rays on the resistance to cancer in mice', Science, 42 (1915), 842. 1915-01-01T00:00:00+0000Stern was the first to describe how a healthy cell changes into a cancerous cell. Her work helped transform cervical cancer into an easily diagnosed and treatable condition. She also demonstrated the links between the herpes simplex virus and cervical cancer and between cervical cancer and the oral contraceptive pill.1915-09-19T00:00:00+0000The trials were carried out by James B Murphy and colleagues at the Rockefeller Institute. 1916-01-01T00:00:00+0000A geneticist by training, Sager enjoyed two careers. She first made her mark in the 1950s and 1950s when she discovered the transmission of genetic traits through chloroplast DNA. This was the first example of genetics not involving the cell nucleus. Later on she became a major pioneer in cancer genetics in the early 1970s and was one of the first to propose and investigate the function of tumour suppressor genes. 1918-02-07T00:00:00+0000E. Freund, G. Kaminer, Wiener Klinische Wochenschrift, Jan 19241924-01-01T00:00:00+0000Fibiger published the first randomisation method for a clinical trial. The aim of the trial, conducted in 1898, was to investigate the effect of serum therapy on diphtheria. Fibiger would later go on to win the 1926 Nobel Prize for Medicine for demonstrating a roundworm could cause stomach cancer in rats and mice. Following his death researchers showed that the roundworm could not cause cancer and were due to vitamin deficiency and that Fibiger had mistakenly confused non-cancerous tumours for cancerous tumours in his experiments.1928-01-30T00:00:00+0000Ames is a biochemist who in the 1970s developed a biological test that makes it possible to quickly and cheaply identify whether or not a chemical compound is a potential carcinogen. Bacteria are exposed to the test substance and allowed to multiply. Before Ames developed his test carcinogenic testing was reliant on using live animals and was a time-consuming and expensive process. 1928-12-16T00:00:00+0000E Witebsky, 'Disponibilitiit und Spezifitat alkoholloslicher Strukturen von Organen und bosartigen Geschwulsten', Zeitschrift fur Imrnunitaetsforschung, Allergie und Klinische Immunologie' 62 (1929), 35-73. 1929-01-01T00:00:00+0000Founded by Clarence Little, one of the leading researchers into genetic differences governing the rejection of foreign tissues. 1929-01-01T00:00:00+0000R Pearl, 'Cancer and tuberculosis', American Journal of Hygiene, 9 (1929), 97-149. 1929-04-01T00:00:00+0000Temin was a geneticist and virologist who shared the 1975 Nobel Prize for Medicine for his work on the interactions between tumour viruses and the genetic material of the cell. In 1969 he demonstrated that certain tumour viruses carry the ability to reverse the flow of information from RNA back to DNA using the enzyme reverse transcriptase. The same enzyme is now is known to be linked to the widespread spread of viral diseases like AIDs and Hepatitis B. 1934-12-10T00:00:00+0000Bishop is an immunologist and microbiologist. He shared the 1989 Nobel Prize for Medicine with Harold E Varmus for discovering the first human oncogene, c-Src. Oncogenes are a type of gene that in certain circumstances, such as exposure to chemical carcinogens, can change a normal cell into a tumour cell. Bishop and Varmus made the discovery while working with the Rouse sarcoma virus known to cause cancer in chickens. 1936-02-22T00:00:00+0000Baltimore shared the 1975 Nobel Prize for his work on the interaction between tumor viruses and the genetic material of the cell. He also spearheaded efforts for the scientific governance of recombinant DNA and genome editing technologies. 1938-03-07T00:00:00+0000Varmus trained as a physician and has spent his career investigating the mechanisms by which retroviruses replicate, cause cancer in animals and produce cancer-like changes in cultured cells. Together with Michael Bishop he showed that cancer genes (oncogenes) can emerge from normal cellular genes, called proto-oncogenes. This they discovered while studying a retroviral gene, v-src, that is responsible for the induction of cancer in chickens by the Rous sarcoma virus. He and Bishop were awarded the Nobel Prize for Medicine for the discovery of the cellular origin of retroviruses in 1989.1939-12-18T00:00:00+0000MK Barrett, 'The influence of genetic constitution upon the induction of resistance to transplantable tumors', Journal of the National Cancer Institute, 2 (1940), 387-93.1940-01-01T00:00:00+0000Levy is an oncologist who in 1981 made history by successfully using monoclonal antibodies to treat the first patient with lymphoma. This work laid the foundation for the development of Rituxan, the first monoclonal antibody drug approved by the FDA for the treatment of cancer. Levy is now focused on the development of cancer vaccines. 1941-12-06T00:00:00+0000The drug emerged out of studies of organic compounds called purines conducted by Gertrude Elion with George Hitchings. Elion hypothesised that by preventing purines entering the metabolic pathway that leads to DNA synthesis it would be possible to stop the production of DNA and thereby stop cell growth. Elion synthesised a forerunner of 6-mercaptopurine in 1949, which was found to inhibit the growth of leukaemia in mice. 1953-01-01T00:00:00+0000Lewis Thomas and Frank MacFarlane Burnet develop a theory that the immune system regularly screens and protects the body against cancer, and that cancer only develops when this mechanism fails. 1957-01-01T00:00:00+0000Found by Charlotte Friend, the virus is now known as Friend leukaemia virus. 1957-01-01T00:00:00+0000Each sick child was terminally ill and chemotherapy was of no further use. Lethal levels of radiation were used to try to eradicate the leukaemia, followed by the infusion of genetically identical marrow (from the healthy twin).1959-01-01T00:00:00+0000Mice injected with BCG vaccine shown to develop resistance to growth of implanted tumours. The finding was published in LJ Old, DA Clarke, B Benacerraf, 'Effect of bacillus calmette-guerin infection on transplanted tumours in the mouse', Nature, 184 (1959), 291-92.1959-07-25T00:00:00+0000The phenomenon was named the 'Hayflick Limit' after Leonard Hayflick who discovered it. It is now known to relate to genetic instability in aging cells and the development of cancer.1961-01-01T00:00:00+0000The finding was based on 10 years of research conducted by Elizabeth Stern with 10,5000 women who used a family planning clinic in Los Angeles. E Stern, PM Neely, 'Carcinoma and Dysplasia of the Cervix: A comparison of rates for new and returning populations', Acta Cytol, 7 (1963), 357-61.1963-01-01T00:00:00+0000LJ Old, EA Boyse, E Oettgen, ED Harven, ED Geering, B Williamson, P Clifford, 'Precipitating antibody in human serum to an antigen present in cultured Burkitt's lymphoma cells', Proc Natl Acad Sci USA, 56 (1966), 1699–1704.1966-12-01T00:00:00+0000I. Hellstrom, K. E. Hellstrom, C. A. Evans, G. Heppaer, G. E. Piece, I. P. S. Yang, 'Serum-mediated protection of neoplastic cells from inhibition by lymphocytes immune to their tumor-specific antigens', PNAS USA, 1969, 62, 362-9.1969-02-01T00:00:00+0000H. O. Sjogren, I. Hellstrom, S. C. Bansal, K. E. Hellstom, 'Suggestive evidence that the blocking antibodies of tumor-bearing individuals may be antigen--antibody complexes', PNAS, USA, 1971, 68/6, 1372-5. 1971-06-01T00:00:00+00001972-01-01T00:00:00+00001972-01-01T00:00:00+0000An American pathologist, Rous won the 1966 Nobel Prize for showing how viruses could cause cancer. He demonstrated this in 1910 by transplanting some material from a cancer tumour taken from a chicken into a healthy chicken. The healthy chicken developed cancer. Other scientists struggled to replicate his experiment in mammals so his discovery was initially dismissed. 1972-02-16T00:00:00+0000The transplant was carried out by Richard O'Reilly and Robert Good. This lays the foundation for the routine use of bone marrow transplants for treating some blood cancers. Such transplants are classed as immunotherapy because immune cells from the donor kill cancer cells in the recipient. 1973-01-01T00:00:00+0000O Stutman, 'Tumor development after 3-methylcholanthrene in immunologically deficient athymic-nude mice', Science, 183 (1974), 534-6.1974-02-08T00:00:00+0000R Kiessling, E Klein, H Pross, H Wigzell, 'Natural” killer cells in the mouse. II. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Characteristics of the killer cell', European Journal of Immunology, 5 (1975), 117-121.1975-02-01T00:00:00+0000M Jondal, H Pross, 'Surface markers on human B and T lymphocytes, Cytotoxicity against cell lines as a functional marker for lymphocyte subpopulations', International Journal of Cancer, 15 (1975) 15, 596-605. 1975-04-15T00:00:00+0000GT Stevenson, F K Stevenson, 'Antibody to a molecularly defined antigen confined to a tumour cell surface', Nature, 254 (1975), 714-16.1975-04-24T00:00:00+0000The marker was found by George and Freda Stevenson, a husband and wife team at the Tenovus Research Laboratory, Southampton University. This they found during investigations of leukaemia in guinea-pigs. They called the marker 'idiotype' because it was identical on every tumour cells but different for every other normal B lymphocytes. Their findings paved the way to development of cancer immunotherapy. The work was published in G T Stevenson, F K Stevenson, 'Antibody to a molecularly-defined antigen confined to a tumour cell surface', Nature, 254 (1975), 714-16. 1975-04-25T00:00:00+0000EA Carswell, LJ Old, RL Kassel, S Green, N Fiore, B Williamson, 'An endotoxin-induced serum factor that causes necrosis of tumors', Proc Natl Acad Sci USA, 72/9 (1975), 3666-70.1975-09-01T00:00:00+0000DA Morgan, FW Ruscetti, RC. Gallo, 'Selective in vitro growth of T lymphocytes from normal human bone marrows', Science, 193 (1976), 1007-08. 1976-09-10T00:00:00+0000JH Robinson, JJT Owen, 'Generation of T-cell function in organ culture of foetal mouse thymus I. Mitogen responsiveness', Clin Exp Immunol 23 (1977), 347-54.1977-02-01T00:00:00+0000FK Stevenson, E V elliott, G T Stevenson, 'Some effects of leukaemic B lymphocytes of antibodies to defined regions of their surface immunoglobulin', Immunology 3 (1977), 54-9.1977-04-01T00:00:00+0000FW Ruscetti, DA Morgan, RC Gallo, 'Functional and morphologic characterization of human T cells continuously grown in vitro', Jounral Immunology, 119 (1977), 131-8.1977-07-01T00:00:00+0000MJ Berendt, RJ North, DP, Kirstein, 'The immunological basis of endotoxin-induced tumor regression: requirement for T-cell-mediated immunity', J Exp Med, 148 (1978), 1550-9. 1978-12-01T00:00:00+0000Six groups of investigators working independently from each other made the discovery. Those involved in the work included Lionel Crawford and David Lane; Albert Deleo and Lloyd Old; and Arnold Levine. 1979-01-01T00:00:00+00001980-01-01T00:00:00+0000Stern, a Canadian born pathologist, was the first to describe how a healthy cell changes into a cancerous cell. Her work helped transform cervical cancer into an easily diagnosed and treatable condition. She also demonstrated the links between the herpes simplex virus and cervical cancer and between cervical cancer and the oral contraceptive pill.1980-08-18T00:00:00+0000The work, led by Beverly Griffin, opened up the possibility of sequencing the virus. It was published in J R Arrand, L. Rymo, J E Walsh, E Bjorck, T Lindahl and B E Griffin, ‘Molecular cloning of the complete Epstein-Barr virus genome as a set of overlapping restriction endonuclease fragments’, Nucleic Acids Research, 9/13 (1981), 2999-2014.1981-07-10T00:00:00+00001982-01-01T00:00:00+0000EA Grimm, A Mazumder, HZ Zhang, SA Rosenberg, 'Lymphokine-activated killer cell phenomenon', Journal Experimental Medicine, 155 (1982), 1823-41.1982-06-01T00:00:00+0000JP Allison, BW McIntyre, D Bloch, 'Tumor-specific antigen of murine T-lymphoma defined with monoclonal antibody', Journal Immunology, 129 (1982), 2293.1982-11-01T00:00:00+0000A N Houghton, M Eisinger, A P Albino, J G Cairncross, L J Old, 'Surface antigens of melanocytes and melanomas. Markers of melanocyte differentiation and melanoma subsets', Journal Experimental Medicine, 156/6 (1982), 1755-66.1982-12-01T00:00:00+0000Based on investigation of blood drawn from AIDS patients who developed Kaposi sarcoma, a cancer caused by a virus. The research was carried out by Susan Krown and Bijan Safai.1983-01-01T00:00:00+0000M Oren, A J Levine, 'Molecular cloning of a cDNA specific for the murine p53 cellular tumor antigen', PNAS, 80 (1983), 56–9. 1983-01-01T00:00:00+0000WHO, WHO Technical Report Series, No. 691 (Geneva: WHO, 1983).1983-01-01T00:00:00+0000GC Bosma, RP Custer, MJ Bosma, 'A severe combined immunodeficiency mutation in the mouse', Nature, 301 (1983), 527-30. 1983-02-10T00:00:00+0000T Taniguchi et al, 'Structure and expression of a cloned cDNA for human interleukin-2', Nature, 302 (1983), 305-10.1983-03-24T00:00:00+0000M Durst, L Gissmann, H Ikenberg, H zur Hausen, 'A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions', Proc Natl Acad Sci USA, 80 (1983), 3812-15.1983-06-01T00:00:00+0000J Kappler et al, 'The major histocompatibility complex-restricted antigen receptor on T cells in mouse and man', Cell, 35 (1983), 295-02. 1983-11-01T00:00:00+0000D Wolf, V Rotter, 'Inactivation of p53 gene expression by an insertion of Moloney murine leukemia virus-like DNA sequences', Mol Cell Biol, 4 (1984), 1402–10. 1984-01-01T00:00:00+0000G Matlashewski, et al, 'Isolation and characterization of a human p53 cDNA clone: expression of the human p53 gene', EMBO Journal, 3 (1984), 3257–62.1984-01-01T00:00:00+0000A Knuth, B Danowski, HF Oettgen, LJ Old, 'T cell-mediated cytotoxicity against malignant melanoma', Proc Natl Acad Sci USA, 81 (1984), 3511-15. 1984-06-01T00:00:00+0000PJ Maddon et al, Cell, 42 (1985), 93-104; Littman et al, Cell, 40 (1985), 237-46. 1985-01-01T00:00:00+0000SA Rosenberg et al, 'Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer', New England Journal of Medicine, 313 (1985), 1485-92.1985-12-05T00:00:00+0000Development of the oncomouse rested on a collaboration initiated by Richard Palmiter and Ralph Brinster in late 1980. The transgenic mouse opened up the means to study oncogene cooperation and the efficacy of novel anti-cell signal drugs for lymphoma therapy. It was published in JM Adams, AW Harris, CA Pinkert, LM Corcoran, WS Alexander, S Cory, RD Palmiter, RL, Brinster, 'The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice', Nature, 318 (1985), 533-38.1985-12-12T00:00:00+0000MT Lotze, AE Chang, CA Seipp, C Simpson, JT Vetto, AS Rosenberg, 'High-dose recombinant interleukin 2 in the treatment of patients with disseminated cancer', JAMA, 256 (1986), 3117-24. 1986-12-12T00:00:00+0000The research was led by Thierry Boon and Etienne De Plaen at the Ludwig Institute for Cancer Research, Belgium1987-01-01T00:00:00+0000The clones were isolated from the blood of melanoma patient with long-term remission following vaccination with irradiated mutagenized autologous tumor cells. M Hein et al, 'Production of stable cytolytic T-cell clones directed against autologous human melanoma', International Journal of Cancer, 39 (1987), 390-96. 1987-03-15T00:00:00+0000Z Dembi et al, 'Transfection of the CD8 gene enhances T-cell recognition', Nature, 326 (1987), 510-11.1987-04-02T00:00:00+0000JF Brunet et al, 'A new member of the immunoglobulin superfamily--CTLA-4', Nature 328 (1987), 267-70. 1987-07-16T00:00:00+0000C Doyle, JL Strominger, 'Interaction between CD4 and class II MHC molecules mediates cell adhesion', Nature, 330 (1987), 256-9.1987-11-19T00:00:00+0000USPTO patent 4,736,866 awarded for transgenic mouse with activated oncogenes created by Philip Leder and Timonthy A Stewart at Harvard University. The two scientists isolated a gene that causes cancer in many mammals, including humans, and inserted it into fertilised mouse eggs. The aim was to genetically engineer a mouse as a model for furthering cancer research and the testing of new drugs. It was the first animal ever given patent protection in the USA. 1988-04-12T00:00:00+0000G Degiovanni et al, European Journal Immunology, 18 (1988+), 671-6; Knuth et al, Proc Natl Acad Sci USA, 86 (1989), 2804-08; Van den Eynde et al, International Journal of Cancer, 15 /44 (1989), 634-40. 1988-05-01T00:00:00+0000CE Rudd, JM Trevillyan, JD Dasgupta, LL Wong, SF Schlossman, 'The CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (Pp58) from human T lymphocytes', Proc Natl Acad Sci USA, 85 (1988), 5190-94.1988-07-01T00:00:00+00001988-07-14T00:00:00+0000P Dariavach, MG Mattei, P Golstein, MP Lefranc, 'Human Ig superfamily CTLA-4 gene: chromosomal localization and identity of protein sequence between murine and human CTLA-4 cytoplasmic domains', European Journal Immunology, 18 (1988), 1901-05.1988-12-01T00:00:00+0000SJ Baker et al, 'Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas', Science, 244 (1989), 17-21, 1989; D Eliyahu et al, 'Wild-type p53 can inhibit oncogene-mediated focus formation', PNAS, 86 (1989), 8763–7; CA Finlay et al, 'The p53 proto-oncogene can act as a suppressor of transformation', Cell, 57 (1989), 1083–93.1989-01-01T00:00:00+0000D Malkin et al, 'Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms', Science, 250 (1990), 1233–8; S Srivastava et al, 'Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome', Nature, 348 (1990), 747–9.1989-01-01T00:00:00+0000CV Thompson, T Lindsten, JA Ledbetter, SL Kunkel, SA Young, SG Emerson, JM Leiden, CL June, 'CD28 activation pathway regulates the production of multiple T-cell-derived lymphokines/cytokines', Proc Natl Acad Sci U S A , 86 (1989),1333-7.1989-02-01T00:00:00+0000M Kobayashi, L Fitz, M Ryan, RM Hewick, SC Clark, S Chan, R Loudon, F Sherman, B Perussia, G Trinchieri, ' Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes', Journal Expermental Medicine', 170 (1989), 827-45.1989-09-01T00:00:00+0000V. Greger, E. Passarge, W. Hopping, E. Messmer, B. Horsthemke, 'Epigenetic changes may contribute to the formation and spontaneous regression of retinoblastoma', Human Genetics, 83 (1989), 155–58. 1989-09-01T00:00:00+0000G Gross, T Waks, Z Eshhar, 'Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity (chimeric genes/antibody variable region)', Proc Natl Acad Sci USA, 86 (1989), 10024-8.1989-12-01T00:00:00+0000JM Nigro et al, 'Mutations in the p53 gene occur in diverse human tumour types', Nature, 342 (1989), 705-08.1989-12-07T00:00:00+0000The approval was given based on results from a clinical trial carried out by Harry Herr and Herbert Oettgen. The BCG vaccine stimulates an immune response that targets both the tuberculosis bacteria and bladder cancer cells. 1990-01-01T00:00:00+0000D Michalovitz, O Halevy, M Oren, 'Conditional inhibition of transformation and of cell proliferation by a temperature-sensitive mutant of p53', Cell, 62 (1990), 671–80; WE Mercer et al, 'Negative growth regulation in a glioblastoma tumor cell line that conditionally expresses human wild-type p53', PNAS 87/16 (1990), 6166-70.1990-08-01T00:00:00+0000A team at the at the University of Washington, led by Mary-Claire King, demonstrated that a single gene on chromosome 17, later known as the BRCA1 gene, induced many breast and ovarian cancers. This was a major breakthrough was prior to this most scientists were sceptical of the role played between genetics and complex human disease. The team published their findings in JM Hall, et al, 'Linkage of early-onset familial breast cancer to chromosome 17q21', Science, 250/4988 (1990), 1684-89. 1990-12-21T00:00:00+0000E Yonish-Rouach et al, 'Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6', Nature 352 (1991), 345–7; P Shaw et al, 'Induction of apoptosis by wild-type p53 in a human colon tumor-derived cell line', PNAS, 89 (1992), 4495–9.1991-01-01T00:00:00+0000J Momand et al, 'The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation', Cell, 69 (1992), 1237–45.1992-01-01T00:00:00+0000LA Donehower, 'Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours', Nature, 356 (1992), 215–21.1992-01-01T00:00:00+0000W.F. Zapisek, G.M. Cronin, B.D. Lyn-Cook, L.A. Poirier, 'The onset of oncogene hypomethylation in the livers of rats fed methyl-deficient, amino acid-defined diets', Carcinogenesis, 13/10 (1992), 1869-72.1992-10-01T00:00:00+00001993-01-01T00:00:00+0000G Dranoff, E Jaffee, A Lazenby, P Golumbek, H Levitsky, K Brose, V Jackson, H Hamada, D Pardoll, RC Mulligan, 'Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity', Proc Natl Acad Sci USA, 90 (1993), 3539–43.1993-04-15T00:00:00+0000WS el-Deiry et al, 'WAF1, a potential mediator of p53 tumor suppression', Cell, 75 (1993), 817–25.1993-09-01T00:00:00+0000Temin was an American geneticist and virologist who shared the 1975 Nobel Prize for Medicine for his work on the interactions between tumour viruses and the genetic material of the cell. In 1969 he demonstrated that certain tumour viruses carry the ability to reverse the flow of information from RNA back to DNA using the enzyme reverse transcriptase. The same enzyme is now is known to be linked to the widespread spread of viral diseases like AIDs and Hepatitis B.1994-02-09T00:00:00+0000A Bendelac et al, Science, 263 (1994), 1774-78; A Bendelac et al, Science, 268 (1995), 863-5. 1994-03-25T00:00:00+0000Y Cho, S Gorina, PD Jeffrey, NP Pavletich, 'Crystal structure of a p53 tumor suppressor-DNA complex: understanding tumorigenic mutations', Science, 265 (1994), 346–55.1994-07-01T00:00:00+0000P.W. Laird, L. Jackson-Grusby, A. Fazeli, S. L. Dickinson, W. E. Jung, E. Li, R.A. Weinberg, R. Jaenisch, 'Suppression of intestinal neoplasia by DNA hypomethylation', Cell, 81 (1995),197-205, April 21, 1995,1995-04-21T00:00:00+0000The work was led by Padmanee Sharma. The team's finding appeared in P. Sharma et al, ‘Thymus-leukaemia antigen interacts with T cells and self-peptides’, Journal Immunology, 156 (1996), 987-96.1996-02-01T00:00:00+0000DR Leach, MF Krummel, JP Allison, 'Enchancement of antitumor immunity by CTLA-4 blockade', Science, 271/5256 (1996), 1734-36. The discovery laid the foundation for the development immune checkpoint inhibitor drugs to unleash the immune system's destruction of cancer. 1996-03-22T00:00:00+0000B Bogen, 'Peripheral T cell tolerance as a tumor escape mechanism', European Journal Immunology, 26 (1996), 2671-79.1996-11-01T00:00:00+0000Huggins was a Candian surgeon and medical researcher who shared the 1966 Nobel Prize for showing the relationship between certain hormones and certain cancers. In 1941 he demonstrated that it was possible to slow down the growth of prostrate cancer using oestrogen, a female hormone. This is now a common method for treating prostrate cancer. Later on Huggins showed that it was possible to slow down some breast cancers by removing the ovaries and adrenal glands which produce oestrogen. Drugs to block the body's production of oestrogen are now routinely used for treating breast cancer.1997-01-12T00:00:00+0000M Serrano et al, 'Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a', Cell, 88 (1997), 593–602.1997-03-01T00:00:00+0000A geneticist by training, Sager enjoyed two careers. She first made her mark in the 1950s and 1950s when she discovered the transmission of genetic traits through chloroplast DNA. This was the first example of genetics not involving the cell nucleus. Later on she became a major pioneer in cancer genetics in the early 1970s and was one of the first to propose and investigate the function of tumour suppressor genes. 1997-03-29T00:00:00+0000The drug is a monoclonal antibody that targets cancer cells that overproduce the HER2/neu oncoprotein1998-01-01T00:00:00+0000M. Toyota, N. Ahuja, M. Ohe-Toyota, J.G. Herman, S.B. Baylin, J-P.J. Issa, 'CpG island methylator phenotype in colorectal cancer', PNAS, 96/15 (1999), 8681–86.1999-07-20T00:00:00+0000Launched by the biotechnology company Medarex in collaboration with Jim Allison. 2000-01-01T00:00:00+0000Research led by Rajasekharan Somasundaram and Dorothee Herlyn published in Cancer Research.2002-09-14T00:00:00+0000Y. Iwai, M. Ishida, Y. Tanaka, T. Okazaki, T. Honjo, N. Minato, 'Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade', PNAS USA, 99/19 (2002), 12293-7.2002-09-17T00:00:00+00002003-01-01T00:00:00+0000Z. Cui, M. C. Willingham, A. Hicks et al, 'Spontaneous regression of advanced cancer: Identification of a unique genetically determined, age-dependent trait in mice', PNAS, 100/11 (2003), 6682-7. 2003-03-19T00:00:00+0000Padmanee Sharma et al, ‘Frequency of NY-ESO-1 and LAGE-1 expression in bladder cancer and evidence of a new NY-ESO-1 T-cell epitope in a patient with bladder cancer’, Cancer Immunology, 3 (Dec 13 2003), 19.2003-12-13T00:00:00+0000AA Sablina, et al, 'The antioxidant function of the p53 tumor suppressor', Nature Medicine, 11 (2005), 1306–13.2005-12-01T00:00:00+0000Anti-cancer effect pinpointed to macrophages, natural killer cells and neutrophils. This was surprising because before this such white blood cells were assumed to only be effective against bacteria and fungal organisms. Now seen to provide immunity against cancer. A.M. Hicks, G. Redlinger, M.C. Willingham et al, 'Transferable anticancer innate immunity in spontaneous regression/complete resistance mice', PNAS, 103/20 (2006), 7753-58.2006-03-28T00:00:00+0000Drug made by Merck & Co2006-10-06T00:00:00+0000Research conducted by collaboration between Wistar Institute and Vienna Biocenter, published in 'Nature'.2006-11-15T00:00:00+0000A Ventura, et al, 'Restoration of p53 function leads to tumour regression in vivo', Nature, 445 (2007), 661-5; W Xue, et al, 'Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas', Nature, 445 (2007), 656–60.2007-01-01T00:00:00+0000Results presented by Zheng Cui to third conference on 'Strategies for Engineered Negligible Senescence' held at Queen’s College Cambridge, UK.2007-09-20T00:00:00+0000Research led by Emmanuel Skordalakes published in the journal 'Structure'. 2007-11-13T00:00:00+0000Meta-analysis of prospective trials with 6007 patients showed stem cell transplants improved the survival rates of people with acute myeloid leukaemia (the most common form of acute leukaemia) and advocated the use of stem cell transplants become a standard treatment for some patients. J. Koreth et al, 'Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: systematic review and meta-analysis of prospective clinical trials', JAMA, 301/22 (2009), 349-61. 2009-06-10T00:00:00+00002009-11-01T00:00:00+0000The drug was approved for the treatment of unresectable or metastatic melanoma. The drug uses a monoclonal that blocks CTLA-4 so as to activate an immune response against the cancer.2011-03-25T00:00:00+0000Dulbecco was an Italian American who shared the 1975 Nobel Prize for Medicine for 'discoveries concerning the interaction between tumour viruses and the genetic material of the cell.' His work not only aided better understanding of how viruses cause cancer but also HIV. 2012-02-19T00:00:00+0000Emily Whitehead, aged 6, was the first child ever to be given the genetically altered T cells. She experienced severe side effects, including raging fever, dramatic drop in blood pressure, lung congestion, but emerged cancer free. Treatment was led by Carl June. Engineering the T cells was estimated to cost $20,000 per patient. 2012-04-01T00:00:00+00002012-09-28T00:00:00+0000The drug was developed by scientists at Medarex2014-09-01T00:00:00+0000The drug (nivolumab, Opdivo®), a monoclonal antibody, was approved by the FDA for the treatment of patients with melanoma. The foundation for the drug was laid by the discovery by of the PD-1 protein in 1992 and the work of Gordon Freeman and his team at Dana-Faber Institute which showed that cancer cells can hijack the protein to evade attack by the immune system. 2014-12-22T00:00:00+00002015-04-01T00:00:00+0000Rose was an American biochemist who shared the 2004 Nobel Prize for Chemistry for contributing to understandings about how cells break down proteins. He first became interested in the puzzle of how cells identify and destroy unwanted proteins in the 1950s. In the late 1970s he showed that ubiquitin, a protein present in countless tissues, helped tag other proteins that needed to be destroyed. It would then attach itself to another protein that was no longer functioning and take it to the proteasome chamber to be broken down and recycled. Rose also helped in the development of a drug to treat multiple myeloma, a blood cancer. The drug works by disrupting the protein disposal mechanism and kills the cancer cells with a pile-up of protein. 2015-06-03T00:00:00+0000The drugs use a monoclonal antibody to block a protein known as PD-1, which functions as an immune checkpoint, being responsible for preventing the activation of T-cells. Promising results were presented to American Society for Clinical Conference from trials directed towards treating lung and skin cancer. 2015-06-05T00:00:00+0000K.B. Chiappinelli, P.L. Strissel, A. Desrichard, et al, 'Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses', Cell, 162 (2015), 974-86.2015-08-27T00:00:00+0000Research conducted by team led by immunologist Laurence Zitvogel. M. Vetizou et al, 'Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota', Science, 350/6264, (2015), 1079-84. doi: 10.1126/science.aad1329.2015-11-27T00:00:00+0000Based on the analysis of data from hundreds of patients, scientists found markers on tumour cells flagging up very early mutations of the disease. The advantage is these appear on all tumour cells, thereby providing a good target for treatment. N. McGranahan, et al, 'Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade', Science, 351/6280 (2016), 1463-69. 2016-03-25T00:00:00+0000UK scientists show how the TALENs gene editing tool can be used to switch on the immune system to stop cancer. L. Menger, et al, 'TALEN-Mediated Inactivation of PD-1 in Tumor-Reactive Lymphocytes Promotes Intratumoral T-cell Persistence and Rejection of Established Tumors', Cancer Research, 2016, doi: 10.1158/0008-5472.CAN-15-3352. 2016-04-15T00:00:00+0000The drug was developed by Genetech/Roche2016-05-01T00:00:00+0000Research carried out by a team led by Dimitry I Gabriolvich. 2016-08-05T00:00:00+0000It was the first time tyhe FDA approved an immune checkpoint inhibitor for the treatment of lung cancer. The drug was developed by Merck & Co.2016-10-24T00:00:00+0000Announcement based on study of 221 patients with metastatic melanoma, approximately half of whom were treated with a PD1 checkpoint inhibitor drug. The research was conducted by researchers led by Jennifer Wargo at the University of Texas MD Anderson Cancer Center. V. Gopalakrishnan et al, ASCO-SITC Clinical Immuno-Oncology Symposium. Abstract 02. Presented February 24, 2017. 2017-02-24T00:00:00+0000Developed by EMD Serono, avelumab was the first FDA approved product to treat metastatic Merckel cell carcinoma. Approval was given on the basis of basis of a clinical trial of 88 patient, 33% of whom experienced a complete or partial shrinkage of their tumours. In patients who responded, 86% had a response that last 6 months, and 45% had a response that lasted more than 12 months. The drug is being developed through an alliance between Merck KGaA and Pfizer. 2017-03-23T00:00:00+0000The drug CTL019 (tisagenlecleucel) was developed by Novartis. Treatment involves removing T cells from the patient and genetically modifying them to increase their capacity to bind to tumour cells in order to get the immune sytem to attack the tumours. It is targeted at children and young adults from three to 25 years old who have not responded to traditional treatments.2017-07-12T00:00:00+0000The drug Kymriah (tisagenlecleucel) is the first gene therapy to become available in the US. 2017-08-30T00:00:00+0000Research conducted by team led by Laurence Zitvogel at the Gustave Roussy Cancer Institute. B.Routy, 'Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors', Science, eaan3706 DOI: 10.1126/science.aan37062017-11-02T00:00:00+0000Collaborative study led by Jennifer Wargo and Vancheswaran Gopalakrishnan. V. Gopalakrishnan et al, 'Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients', Science, 2 Nov 2017, eaan4236, DOI: 10.1126/science.aan42362017-11-02T00:00:00+0000The test detects circulating tumour DNA. It was investigated using blood samples from 161 patients with stage 2 and 3 melanoma who had received surgery. Results showed that skin cancer was much more likely to return within a year of surgery in patients with faults in either BRAF or NRAS genes. R J Lee et al, 'Circulating tumor DNA predicts survival in patients with resected high-risk stage II/III melanoma', Annals of Oncology, mdx717, https://doi.org/10.1093/annonc/mdx7172017-11-03T00:00:00+0000The test hunts for 16 gene that regularly arise in cancer and 8 proteins released by tumours. It was trialled in 1,005 patients with cancers of the ovary, liver, stomach, pancreas, oesophagus, colon, lung or breast that had not yet spread to other tissues. J.D. Cohen et al, Detection and localization of surgically resectable cancers with a multi-analyte blood test', Science, 18 Jan 2018, eaar3247, DOI: 10.1126/science.aar3247 2018-01-17T00:00:00+0000Allison helped to demonstrate the importance of blocking CTLA-4, a protein found on T-cells, for cancer treatment, which laid the foundation for the development of ipilimumab. Honjo discovered, PD-1, another type of protein found on T-cells which cancer cells were subsequently discovered to hijack to evade attack by the immune system. 2018-10-01T00:00:00+0000
Date Event People Places
23 Apr 1867Johannes A G Fibiger was born in Silkeborg, DenmarkFibigerSilkeborg, Denmark
5 Oct 1879Francis Peyton Rous was born in Baltimore MD, USARousRockefeller University
May 1893First successful treatment of cancer patient with immunotherapyColeyMemorial Sloan Kettering Cancer Center
1895Humans treated with antiserum prepared against human cancer. This established the principle of using serotherapy to fight cancerHericourt, RichetCollege de France
1899First commercial vaccine developed for treatment of sarcomaColeyMemorial Sloan Kettering Cancer Center, Parke Davis & Co
1901 - 1903First successful transplants of tumours in animals reported, providing a new experimental system for studying the role of the immune system in cancerLeob, JensenUniversity of Pennsylvania, Agriculture and Veterinary Institute
22 Sep 1901Charles B Huggins was born Halifax, CanadaHugginsUniversity of Chicago
1902First attempt to vaccinate against cancer with a patient's own tumour tissuevon Leyden, Blumenthal 
1910Austrian physicians Ernest Freund and Gisa Kaminer observed that something in blood serum from cancer patients pervents the destruction of cancer cellsFreund, KaminerRudolf-Stiftung Hospital
1911Research provided the first evidence that virus transmits cancer in chickensRousRockefeller Institute
1914Experiments by James B Murphy demonstrate that lymphocytes help animals reject grafted tumoursMurphyRockefeller Intitute
22 Feb 1914Renato Dulbecco was born in Catanzaro, ItalyDulbeccoImperial Cancer Research Fund Laboratory
1915 James B Murphy puts forward hypothesis that the nonspecific stimulation of lymphocytes could provide a cure for cancer based on experiments he and John J Morton carried out on miceMurphy, MortonRockefeller Institute
19 Sep 1915Elizabeth Stern was born in Cobalt, Ontario, CanadaSternUniversity of California at Los Angeles
1916 - 1922Disappointing results reported from clinical trials treating breast cancer patients with low doses of X-ray radiation following tumour removal, discrediting the theory that stimulation of lymphocytes could help cure cancer. MurphyRockefeller Institute
7 Feb 1918Ruth Sager was born in Brookline, Massachusetts, USASagerRockefeller University
1924Austrian physicians Ernest Freund and Gisa Kaminer discover a substance in intestines of cancer patients that reduce ability of normal serum to dissolve cancer cells. Freund, KaminerRudolf-Stiftung Hospital
30 Jan 1928Johannes Fibiger diedFiber 
16 Dec 1928Bruce N Ames was born in New York, USAAmesUniversity of California Berkeley
1929First molecular marker, antigen, identified on a tumour, laying foundation for use of antibodies to diagnose and treat cancerWitebsky University of Heidelberg
1929Jackson Memorial Laboratories established to develop inbred strains of mice to study the genetics of cancer and other diseasesJackson Memorial Laboratoroies
April 1929Autopsies carried out on tuberculosis patients show them less likely to have contracted cancerPearlJohns Hopkins University
10 Dec 1934Howard M Temin was born in Philadelphia, PA, USATeminUniversity of Wisconsin
22 Feb 1936John Michael Bishop born in York PA, USABishopUniversity California San Francisco
7 Mar 1938David Baltimore was born in New York CityBaltimoreNew York City
18 Dec 1939Harold E Varmus was born in Oceanside NY, USAVarmusUniversity of California San Francisco
1940Inbred strains of mice bred at Jackson Memorial Laboratory showed that resistance to transplanted tumours were due to body's resistance to genetically different tissueBarrettJackson Memorial Laboratoroies
6 Dec 1941Ronald Levy was born in Carmel, California, United StatesLevyStanford University
1953FDA approved 6-mercaptopurine as treatment for childhood leukaemiaElion, HitchingWellcome Research Laboratories
1957 - 1959Concept developed that the immune system naturally protects against cancerBurnet, Lewis 
1957Leukaemia virus found, reinforcing idea that viruses can cause cancerFriendMemorial Sloan Kettering Cancer Center
1959Bone marrow transplants in two sets of identical twin girls fails to eradicate leukaemiaThomas, Ferrebee, Sahler Bassett Medical Center
25 Jul 1959First direct evidence of the immune system's ability to prevent cancer provided by Lloyd Old and colleaguesOld, Clarke, BenacerrafMemorial Sloan Kettering Cancer Center
1961Normal cell population discovered to only be able to divide a limited number of times before it stopsHayflickWistar Institute
1963First report linking a specific virus (herpes simplex virus) to a specific cancer (cervical cancer)SternUniversity of California, Los Angeles
December 1966Scientists detect antibodies to the Epstein-Barr virus in patients with nasopharyngeal cancer which suggest the cancer is caused by a virus. Old, Boyse, OettgenMemorial Sloan Kettering Cancer Center
February 1969Team led by Karl and Ingegerd Hellstrom observe serum from mice with chemically induced tumours can block reaction of lymphocytesHellstrom, Evans, Heppner, Pierce, Yang Fred Hutchinson Cancer Center
June 1971Hellstom team suggest that antibodies bound to tumour cells mask their detection by the immune system Sjogren, Hellstrom, BansalFred Hutchinson Cancer Center
1972US National Cancer Institute recommended creation of international registry of immunotherapy trials 
1972Wistar Instute named National Cancer Institute - first research institution to gain such a titleWistar Institute
16 Feb 1972Francis Peyton Rous diedRousRockefeller University
1973First successful bone marrow transplant from unrelated donorGood, O'ReillyMemorial Sloan Kettering Cancer Center
8 Feb 1974Immune surveillance theory that immune system provides protection against cancer discredited by research showing that 'Nude' mice lacking immune system function no more likely to develop tumours than normal miceStutmanMemorial Sloan-Kettering Cancer Center
February 1975Natural killer cell identified in mice and shown to be important part of immune systemKiessling, Klein, Pross, WigzellKarolinska Institute
15 Apr 1975Human natural killer cell isolatedJondal, ProssKarolinska Institute
24 Apr 1975Discovery of unique molecular marker, idiotype, on blood cancer cells, opening new avenue for cancer diagnosis and therapyStevensonTenovus Research Laboratory
25 Apr 1975Unique 'idiotype' marker discovered on the surface of proteins in cancer cells, providing target for treating cancer with antibodiesStevensonSouthampton University
September 1975Tumour necrosis factor (TNF) was discovered. It was the first immune molecule shown to kill cancer cellsCarswell, Old, Kassel, S.Green, Fiore, WilliamsonMemorial Sloan Kettering Cancer Center
10 Sep 1976Discovery of first T cell growth factor, later named Interleukin-2 (IL-2)Morgan, Ruscetti, GalloLitton Bioethics Research Laboratories, National Cancer Institute
February 1977Scientists find a way to generate T cells in thymic tissue in test tubes, paving the way study mechanisms underlying the regulation of T cell developmentRobinson, OwenUniversity of Newcastle upon Tyne
1 Apr 1977Development of first anti-idiotype antibodies. These are shown to activate immune defense cells to attack tumour cells in guinea-pigsStevenson, ElliottTenovus Research Laboratory
July 1977T cell growth factor, later named Interleukin-2 (IL-2), discovered in mice, providing a means to grow and expand normal lypmphocytes in test tubesRuscetti, Morgan, GalloNational Cancer Institute
1978T cell-mediated immunity shown to aid tumour regressionBerendt, North, KirsteinTrudeau Institute
1979The first tumour suppressor gene was discovered, known as p53Crawford, Lane, Deleo, Old, Levine 
1980US National Cancer Institute added $13.5 million to its budget for new Biological Response Modifiers, igniting search for agents able to modify host's response to tumour cells 
18 Aug 1980Elizabeth Stern diedSternUniversity of California at Los Angeles
10 Jul 1981Complete library of overlapping DNA fragments of Epstein Barr Virus clonedGriffin, Arrand, Walsh, Bjorck, RymoImperial Cancer Research Fund Laboratories, University of Gothenberg
1982Azacitidine fails to win FDA approval for treatment of acute myelogenous leukaemia due to lack of controlled studies showing clinical benefit 
June 1982Steven Rosenberg and colleagues first describe lymphokine-activated killer cellsGrimm, Mazumder, Zhang, RosenbergNational Cancer Institute
November 1982James Allison and collegues use monoclonal antibody to provide first biochemical description of tumour specific antigen of murine T-lymphomaAllison, McIntyre, BlochUniversity of Texas System Cancer Center
1 Dec 1982First molecular markers, antigens, identified in melanoma tumours. These markers are now targeted by cancer drugsHoughton, Eisinger, Albino, Cairncross, OldMemorial Sloan Kettering Cancer Center
1983Link drawn between immune deficiency and cancer Memorial Sloan Kettering Cancer Center
1983Murine p53 gene clonedLevine, OrenWeizmann Institute, State University New York
1983WHO argued hepatitis B virus second only to tobacco as cause of cancer 
10 Feb 1983Discovery of mouse strain with severe combined immune deficiency, providing valuable research model for investigating diseases like cancer and HIVBosma, CusterFox Chase Cancer Center
24 Mar 1983First cloning of Interleukin 2 (Il-2)Taniguchi, Matsui, Fujita, Takaoka, Kashmina, Yoshimoto, HamuroJapanese Foundation for Cancer Research, Ajinomoto Co Inc
June 1983Harald Zur Hausen identifies the human papillomavirus as the causative agent of cervical cancerzur HausenUniversity of Freiberg
November 1983A team of researchers including Philippa Marrack, John Kappler and James P Allison identified the first T cell antigen receptorKappler, Kubo, Haskins, Hannum, Marrack, Pigeon, McIntyre, Allison, TrowbridgeUniversity of Colorado, University of Texas System Cancer Center, National Jewish Hospital and Research Cener, Salk Institute
1984p53 inactivated in tumour cells for first timeWolf, RotterWeizmann Institute
1984Human p53 gene clonedMatlashewski, Lamb, Pim, Peacock, Crawford, BenchimoImperial Cancer Research Fund Laboratories, Ontario Cancer Institute, University of Toronto
June 1984First clinical experiments demonstrate the possibility of training T cells to attack tumoursKnuth, Danowski, Oettgen, OldMemorial Sloan-Kettering Cancer Center
1985T cell surface proteins CD4 and CD8 cloned Maddon, Littman, Godfrey, Maddon Chess, AxelColumbia University
December 1985IL-2 based immunotherapy shown to reduce tumours in patients with melanoma and renal cell cancerRosenbergNational Cancer Institute
12 Dec 1985New transgenic mouse model announced for studying cancerAdams, Harris, Pinkert, Corcoran, Alexander, Cory, Palmiter, BrinsterWalter and Eliza Hall Institute, University of Pennsylvania, Howard Hughes Medical Institute
December 1986Anti-tumour responses observed in 3 out of 10 patients given high-doses of Interleukin-2 (IL-2) Rosenberg, Lotze, Chang, Seipp, Simpson, VettoNational Cancer Institute
1987 - 1989Scientists lay the foundation for the cloning of human tumour antigens recognised by cytotoxic T lymphocytes, a type of white blood cell that kills cancer cellsDe Plaen, BoonLudwig Institute for Cancer Research
15 Mar 1987First stable human anti-tumour cytotoxic T cell clones isolated and maintained in cultureHerin, Lemoine, Weynants, Vessiere, Van Pel, Knuth, Devos, BoonLudwig Institute
April 1987CD8 coreceptor proven to be actively involved in antigen recognition by killer T cellsDembic, Haas, Zamoyska, Parnes, Steinmetz, von BoehmerBasel Institute of Immunology
July 1987Identification of the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)Brunet, Denizot, Luciani, Roux-Dosseto, Suzan, Mattei, GolsteinINSERM-CNRS
November 1987First evidence provided for the interaction between the surface molecule CD4 and major histocompatibility class IIDoyle, StromingerHarvard University
12 Apr 1988OncoMouse patent grantedLeder, StewartHarvard University
May 1988 - Oct 1989Cytotoxic T lymphocytes shown to recognise distinct surface markers on human melanomaWolfel, Knuth, Degiovanni, Van den Eynde, Hainaut, BoonLudwig Institute for Cancer Research
July 1988Biochemical initiators of T Cell activitation, CD4 and CD8-p56, discoveredRudd, Trevillyan, Dasupta, Wong, SchlossmanDana-Faber Cancer Institute, Harvard University, Tech University
1988 - 1989First evidence discovered of a physical link between oncoproteins and tumour suppressors 
December 1988Scientists report cloning the gene for the human cytotoxic T lymphocyte-associated antigen (CTLA-4)Dariavach, Mattei, Golstein, LefrancINSERM-CNRS
1989p53 demonstrated to be a tumour suppressor geneBaker, Fearon, Nigro, Hamilton, Preisinger, Jessup, vanTuinen, Ledbetter, Barker, Nakamura, White, Vogelstein, Eliyahu, Michalovitz, Pinhasi-Kimhi, Oren, Finlay, Hinds, Levine Johns Hopkins University, Weizmann Institute, Princeton University
1989Mutations in p53 found in germline of cancer-prone familiesMalkin, Srivastava, Zou, Pirollo, Blattner, ChangMassachusetts General Hospital, Uniformed Services University
February 1989Scientists demonstrate the importance of CD28, a cell surface molecule found on T-cells, for the activation and survival of T cellsThompson, Lindsten, Ledbetter, Kunkel, Young, Emerson, Leiden, JuneHoward Hughes Medical Institute
September 1989Giorgio Trinchieri and colleagues identified interleukin-12 (IL-12), a cytokine that helps regulate the body’s resistance to infections and cancerKobayashi, Fitz, Ryan, Hewick, Clark, Chan, Loudon, Sherman, Perussia, TrinchieriWistar Institute
September 1989DNA methylation suggested to inactivate tumour suppressor genesGreger, Passarge, Hopping, Messmer, HorsthemkeInstitute of Human Genetics
December 1989First use of genetically engineered T cells to redirect T cells to recognise and attack tumour cellsGross, Waks, EshharWeizmann Institute
7 Dec 1989Mutations in p53 gene found to play role in development of many common cancersVogelstein, NigroJohns Hopkins University
1990US FDA approved BCG, a bacterial vaccine against tuberculosis, to treat early stage bladder cancer. It was the first FDA approved immunotherapyHerr, OettgenMemorial Sloan Kettering Cancer Center
August 1990p53 found to arrest cell cyleMichalovitz, Halevy, Oren, Mercer, Shields, Amin, Sauve, Appella, Romano, UllrichWeizmann Institute, Temple University
21 Dec 1990BRCA1 gene linked with inherited predisposition to cancerKingUniversity of California Berkley
1991p53 found to induce apoptosis, self destruction of a cellYonish-Rouach, Resnitzky, Lotem, Sachs, Kimchi, OrenWeizmann Institute
1992MDM2, an oncogene product, found to negatively regulate p53Momand, Zambetti, Olson, George, LevinePrinceton University
1992Mice genetically modified to be deficient in p53 shown to be prone to cancerDonehower, Harvey, Slagle, McArthur, Montgomery, Butel, BradleyBaylor College
1 Oct 1992First experimental evidence showing links between diet and DNA methylation and its relationship with cancerZapisek, Cronin, Lyn-Cook, PoirierFDA, National Center for Toxicological Research
1993Wistar Institute patented Bcl-2, the first of a family of genes associated with different types of cancerWistar Institute
15 Apr 1993Immune molecule, granulocyte-macrophage colony stimulating factor or GM-CSF, discovered to strengthen immunity against tumours Dranoff, Jaffee, Lazenby, Golumbek, Levitsky, Brose, Jackson, Hamada, Pardoll, MulliganMassachusetts Institute of Technology
September 1993p21 shown to be a p53 target geneel-Deiry, Tokino, Velculescu, Levy, Parsons, Trent, Lin, Mercer, Kinzler, Vogelstein Johns Hopkins University, National Center for Human Genome Research, Thomas Jefferson University
9 Feb 1994Howard M Temin diedTeminUniversity of Wisconsin
1994 - 1995Identification and characterisation of the natural killer T cell, a lymphocyte able to bind and kill certain tumour and virus-infected cellsBendelacUniversity of Chicago
July 1994DNA structure of p53-DNA elucidatedCho, Gorina, Jeffrey, PavletichMemorial Sloan-Kettering Cancer Center
21 Apr 1995First evidence published to demonstrate reduced DNA methylation contributes to formation of tumoursLaird, Jackson-Grusby, Fazeli, Dickinson, Jung, Li, Weinberg, JaenischMassachusetts Institute of Technology, Massachusetts General Hospital
1 Feb 1996Paper published indicating thymus-leukaemia antigen, a cell-surface marker, stimulates T cells to destroy specific target cellsSharmaPennsylvania State University
22 Mar 1996Mice experiments published demonstrating that blocking the CTLA-4 molecule on immune cells can cure cancerLeach, Krummel, AllisonUniversity of California Berkeley
November 1996Experiments demostrate antigen-specific CD4+ and T cells become tolerant during tumour growth in test tubes 
12 Jan 1997Charles B Huggins diedHugginsUniversity of Chicago
March 1997p53 shown to be linked to senescence, biological agingSerrano , Lin, McCurrach, Beach, Lowe Cold Spring Harbor Laboratory
29 Mar 1997Ruth Sager diedSagerRockefeller University
1998FDA approved Trastuzumab (Herceptin) for the treatment of metastatic breast cancer  
20 Jul 1999DNA methylation of CpG islands shown to be linked to colorectal cancerToyota, Ahuja, Ohe-Toyota, Herman, Baylin, IssaJohns Hopkins University
2000First clinical trials launched to test first immune checkpoint inhibitor drug containing a monoclonal antibody against CTLA-4 (ipilimumab, Yervoy®)AllisonMedarex, University of California Berkley
14 Sep 2002Regulatory T cells discovered to restrain cytolytic T cells attacking cancer via messanger chemical called TGF-betaHerlyn, SomasundaramWistar Institute
17 Sep 2002Cancer cells shown to be capable of hijacking PD-1 protein to evade destruction by immune systemIwai , Ishida, Tanaka, Okazaki, Honjo, MinatoJapan Science and Technology Corporation
1 Jan 2003Sharma received ASCO Young Investigator Award to carry out clinical trials with NY-ES0-1 cancer vaccineSharmaMemorial Sloan-Kettering Cancer Center
19 Mar 2003Mutant mouse discovered capable of warding off aggressive cancer and its offspring found to confer resistance to cancer in 40% of his offspringCui, Willingham, Hicks, Alexander-Miller, Howard, Hawkins, Millier, Weir, Du, DeLongWake Forest University
13 Dec 2003Sharma discovered some bladder cancer cells expressed the marker NY-ESO-1 providing means for cancer vaccineSharmaMemorial Sloan-Kettering Cancer Center
December 2005p53 found to have antioxidant functionSablina, Budanov, Ilyinskaya, Agapova, Kravchenko, ChumakovLerner Research Institute
28 Mar 2006Normal mice shown to become resistant to cancer when injected with white blood cells taken from mutant mice known to ward off aggressive cancer. Hicks, Redlinger, Willingham, Alexander-Miller, Kap-Herr, Pettenati, Sanders, Weir, Du, Kim, Simpson, Old, CuiWake Forest University, Ludwig Institute for Cancer Research
6 Oct 2006FDA approved first histone deacetylase inhibitor, Vorinostat (Zolinza), for cutaneous T-cell lymphoma 
15 Nov 2006New enzyme identified as suppressor of p53 protein, a key molecule for controlling cancer in humansBergerWistar Institute, Vienna Biocenter
2007p53-induced senescence shown to prevent cancerVentura, Kirsch, McLaughlin, Tuveson, Grimm, Lintault, Newman, Reczek, Weissleder, Jacks, Xue, Zender, Miething, Dickins, Hernando, Krizhanovsky, Cordon-Cardo, LoweMassachusetts Institute of Technology, Massachusetts General Hospital, Harvard University, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory
20 Sep 2007Experiments in mice indicate cancer-killing capacity of granulocytes, white blood cells taken from humansCuiWake Forest University
13 Nov 2007Inappropriate activation of telomerase, an enzyme, shown to be associated with uncontrollable proliferation of cells seen in human cancersSkordalakesWistar Institute
10 Jun 2009Stem cell transplants reported to improve survival for leukaemia patientsKoreth, Schlen, Kopecky, Honda, Sierra, Djulbegovic, Wadleigh, DeAngelo, Stone, Sakamaki Appelbaum, Dohner, Antin, Soiffer, CutlerDana Farber Cancer Institute
November 2009FDA approved second histone deactylase inhibitor, Romidepsin (Istodax), for cutaneous T-cell lymphoma  
25 Mar 2011First immune checkpoint inhibitor drug targeting CTLA4 (ipilimumab, Yervoy®), approved by the FDAAllisonMedarex, University of California Berkley
19 Feb 2012Renato Dulbecco diedDulbeccoImperial Cancer Research Fund Laboratory
April 2012First child with leukaemia treated with adoptive cell therapy (CAR-T therapy)June, WhiteheadChildren's Hospital of Philadelphia, University of Pennsylvania
2012European approval of decatabine (Dacogen) for treatment of acute myeloid leukaemia 
September 2014FDA approved nivolumab (Opdivo®), an immune checkpoint inhibitor targeting PD1, for treating melanoma 
22 Dec 2014First immune checkpoint inhibitor drug targeting PD-1 approved in US Honko, Freeman, LonbergMedarex, Bristol-Myers Squibb, Ono Pharmaceutical, Kyoto University
April 2015Chinese regulatory authorities approved Chidamide, a histone deactylase inhibitor, for peripheral T cell lymphoma 
3 Jun 2015Irwin Rose diedRoseUniversity of California Irvine
5 Jun 2015Two immunotherapy drugs reported to stop cancer cells avoiding destruction by immune system Allison 
27 Aug 2015Experiments with mice showed that azacytidine treatment enhanced the responsiveness of tumors to anti–CTLA-4 therapy 
27 Nov 2015Experiments in mice indicate that a tumour's response to cancer immunotherapy using CTLA-4 checkpoint inhibitor can be improved by changing the gut microbiome Zitvogel, Veitzou, Institut Gustave Roussy
25 Mar 2016Common tags discovered on the surface of cancer cells opening up new avenues for immunotherapyMcGranahan, Furness, Rosenthal, Ramskov, Lyngaa, Saini, Jamal-Hanjani, Wilson, Birkbak, Hiley, Watkins, Shafi, Murugaesu, Mitter, Akarca, Linares, Marafioti, Henry, Van Allen, Miao, Schilling, Schadendorf, Garraway, Makarov, Rizvi,m Snyder, Hellman, MerghUniversity College London, Cancer Research UK, Francis Crick Insitute, Dana-Farber Cancer Institute, Broad Institute, University Duisburg-Essen, Memorial Sloan Kettering Cancer Center, Columbia Univertsity, Weill Cornell Medical College, Harvard Medical S
15 Apr 2016Gene editing used to prompt immune cells to combat cancerQuezada, Johnson, Menger, Sledzinska, Bergerhoff, Vargas, Smith, Poirot, Pule, Hererro, PeggsUniversity College London, Cancer Research UK, Cellectis
1 May 2016FDA approved atezolizumab (Tecentriq®), an immune checkpoint inhibitor targeted at PD1, for the treatment of urothelial carcinoma, the most common form of bladder cancerGenentech, Roche
August 2016Marker identified for myeloid-derived suppressor cells, a type of cell associated with tumour resistance to certain cancer treatmentsWistar Institute
24 Oct 2016FDA approved pembrolizumab (Keytruda®) for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 as determined by an FDA-approved test.Merck
24 Feb 2017Researchers report patients with greater diversity of gut bacteria have better response to cancer immunotherapyWargo, GopalakrishnanMD Anderson Cancer Center
23 Mar 2017FDA granted accelerated approval to avelumab, a PD-L1 checkpoint inhibitor, to treat Merkel cell carcinoma, a rare form of skin cancer treatment, in patients 12 years and older with metastatic Merkel cell carcinoma, a rare form of skin disorderEMD Serono, Merck KGaA, Pfizer
12 Jul 2017US FDA Oncologic Drugs Advisory Committee recommended the approval of the first adoptive cell therapy (CAR-T cell therapy) for B cell acute leukaemiaJuneNovartis, University of Pennsylvania
30 Aug 2017USA FDA approved CAR-T therapy for certain pediatric and young adult patients with a form of acute lymphoblastic leukemiaJuneNovartis, University of Pennsylvania
2 Nov 2017Cancer patients taking routine antibiotics before or soon after given PD-1 checkpoint inhibitor found to relapse quicker and have shorter survival timeZitvogel, KroemerInstitut Gustave Roussy
2 Nov 2017Experiments with mice show tumour growth can be reduced by giving faecal transplants from patients who positively responded to cancer immunotherapyWargo, GopalakrishnanMD Anderson Cancer Center, Institute Gustave-Roussy
3 Nov 2017Research showed simple blood test can identify patients at most risk of skin cancer returningLee, Gremel, Marshall, Myers, Fisher, Dunn, Dhomen, Corrie, Middleton, Lorigan, MaraisUniversity of Manchester
17 Jan 2018Blood test detecting mutated DNA and proteins released by tumours shown to pick up early signs of 8 common cancersCohen, Yuxuan Wang, Thoburn, Afsari, Danilova. Douville, Javed, Wong, Mattox, Hruban, Wolfgang, Goggins, Molin, Wang, Roden, Klein, Ptak, Dobbyn, Schaefer, Silliman, Popoli, Vogelstein, Browne, Schoen, Brand, Tie, Gibbs, Wong, Mansfield, Jen, Hanash, FalcJohns Hopkins University
1 Oct 2018James Allison and Tasuku Honjo were awarded the Nobel Prize in Physiology or Medicine for their discovery of immune checkpoint inhibitors for cancer therapyAllison, HonjoUniversity of Texas MD Anderson Cancer Center, Kyoto University

23 Apr 1867

Johannes A G Fibiger was born in Silkeborg, Denmark

5 Oct 1879

Francis Peyton Rous was born in Baltimore MD, USA

May 1893

First successful treatment of cancer patient with immunotherapy

1895

Humans treated with antiserum prepared against human cancer. This established the principle of using serotherapy to fight cancer

1899

First commercial vaccine developed for treatment of sarcoma

1901 - 1903

First successful transplants of tumours in animals reported, providing a new experimental system for studying the role of the immune system in cancer

22 Sep 1901

Charles B Huggins was born Halifax, Canada

1902

First attempt to vaccinate against cancer with a patient's own tumour tissue

1910

Austrian physicians Ernest Freund and Gisa Kaminer observed that something in blood serum from cancer patients pervents the destruction of cancer cells

1911

Research provided the first evidence that virus transmits cancer in chickens

1914

Experiments by James B Murphy demonstrate that lymphocytes help animals reject grafted tumours

22 Feb 1914

Renato Dulbecco was born in Catanzaro, Italy

1915

James B Murphy puts forward hypothesis that the nonspecific stimulation of lymphocytes could provide a cure for cancer based on experiments he and John J Morton carried out on mice

19 Sep 1915

Elizabeth Stern was born in Cobalt, Ontario, Canada

1916 - 1922

Disappointing results reported from clinical trials treating breast cancer patients with low doses of X-ray radiation following tumour removal, discrediting the theory that stimulation of lymphocytes could help cure cancer.

7 Feb 1918

Ruth Sager was born in Brookline, Massachusetts, USA

1924

Austrian physicians Ernest Freund and Gisa Kaminer discover a substance in intestines of cancer patients that reduce ability of normal serum to dissolve cancer cells.

30 Jan 1928

Johannes Fibiger died

16 Dec 1928

Bruce N Ames was born in New York, USA

1929

First molecular marker, antigen, identified on a tumour, laying foundation for use of antibodies to diagnose and treat cancer

1929

Jackson Memorial Laboratories established to develop inbred strains of mice to study the genetics of cancer and other diseases

Apr 1929

Autopsies carried out on tuberculosis patients show them less likely to have contracted cancer

10 Dec 1934

Howard M Temin was born in Philadelphia, PA, USA

10 Dec 1934

John Michael Bishop born in York PA, USA

7 Mar 1938

David Baltimore was born in New York City

18 Dec 1939

Harold E Varmus was born in Oceanside NY, USA

1940

Inbred strains of mice bred at Jackson Memorial Laboratory showed that resistance to transplanted tumours were due to body's resistance to genetically different tissue

6 Dec 1941

Ronald Levy was born in Carmel, California, United States

1953

FDA approved 6-mercaptopurine as treatment for childhood leukaemia

1957 - 1959

Concept developed that the immune system naturally protects against cancer

1957

Leukaemia virus found, reinforcing idea that viruses can cause cancer

1959

Bone marrow transplants in two sets of identical twin girls fails to eradicate leukaemia

25 Jul 1959

First direct evidence of the immune system's ability to prevent cancer provided by Lloyd Old and colleagues

1961

Normal cell population discovered to only be able to divide a limited number of times before it stops

1963

First report linking a specific virus (herpes simplex virus) to a specific cancer (cervical cancer)

Dec 1966

Scientists detect antibodies to the Epstein-Barr virus in patients with nasopharyngeal cancer which suggest the cancer is caused by a virus.

Feb 1969

Team led by Karl and Ingegerd Hellstrom observe serum from mice with chemically induced tumours can block reaction of lymphocytes

Jun 1971

Hellstom team suggest that antibodies bound to tumour cells mask their detection by the immune system

1972

US National Cancer Institute recommended creation of international registry of immunotherapy trials

1972

Wistar Instute named National Cancer Institute - first research institution to gain such a title

16 Feb 1972

Francis Peyton Rous died

1973

First successful bone marrow transplant from unrelated donor

8 Feb 1974

Immune surveillance theory that immune system provides protection against cancer discredited by research showing that 'Nude' mice lacking immune system function no more likely to develop tumours than normal mice

Feb 1975

Natural killer cell identified in mice and shown to be important part of immune system

15 Apr 1975

Human natural killer cell isolated

24 Apr 1975

Discovery of unique molecular marker, idiotype, on blood cancer cells, opening new avenue for cancer diagnosis and therapy

25 Apr 1975

Unique 'idiotype' marker discovered on the surface of proteins in cancer cells, providing target for treating cancer with antibodies

Sep 1975

Tumour necrosis factor (TNF) was discovered. It was the first immune molecule shown to kill cancer cells

10 Sep 1976

Discovery of first T cell growth factor, later named Interleukin-2 (IL-2)

Feb 1977

Scientists find a way to generate T cells in thymic tissue in test tubes, paving the way study mechanisms underlying the regulation of T cell development

1 Apr 1977

Development of first anti-idiotype antibodies. These are shown to activate immune defense cells to attack tumour cells in guinea-pigs

Jul 1977

T cell growth factor, later named Interleukin-2 (IL-2), discovered in mice, providing a means to grow and expand normal lypmphocytes in test tubes

1978

T cell-mediated immunity shown to aid tumour regression

1979

The first tumour suppressor gene was discovered, known as p53

1980

US National Cancer Institute added $13.5 million to its budget for new Biological Response Modifiers, igniting search for agents able to modify host's response to tumour cells

18 Aug 1980

Elizabeth Stern died

10 Jul 1981

Complete library of overlapping DNA fragments of Epstein Barr Virus cloned

1982

Azacitidine fails to win FDA approval for treatment of acute myelogenous leukaemia due to lack of controlled studies showing clinical benefit

Jun 1982

Steven Rosenberg and colleagues first describe lymphokine-activated killer cells

Nov 1982

James Allison and collegues use monoclonal antibody to provide first biochemical description of tumour specific antigen of murine T-lymphoma

1 Dec 1982

First molecular markers, antigens, identified in melanoma tumours. These markers are now targeted by cancer drugs

1983

Link drawn between immune deficiency and cancer

1983

Murine p53 gene cloned

1983

WHO argued hepatitis B virus second only to tobacco as cause of cancer

10 Feb 1983

Discovery of mouse strain with severe combined immune deficiency, providing valuable research model for investigating diseases like cancer and HIV

24 Mar 1983

First cloning of Interleukin 2 (Il-2)

Jun 1983

Harald Zur Hausen identifies the human papillomavirus as the causative agent of cervical cancer

Nov 1983

A team of researchers including Philippa Marrack, John Kappler and James P Allison identified the first T cell antigen receptor

1984

p53 inactivated in tumour cells for first time

1984

Human p53 gene cloned

Jun 1984

First clinical experiments demonstrate the possibility of training T cells to attack tumours

1985

T cell surface proteins CD4 and CD8 cloned

Dec 1985

IL-2 based immunotherapy shown to reduce tumours in patients with melanoma and renal cell cancer

12 Dec 1985

New transgenic mouse model announced for studying cancer

Dec 1986

Anti-tumour responses observed in 3 out of 10 patients given high-doses of Interleukin-2 (IL-2)

1987 - 1989

Scientists lay the foundation for the cloning of human tumour antigens recognised by cytotoxic T lymphocytes, a type of white blood cell that kills cancer cells

15 Mar 1987

First stable human anti-tumour cytotoxic T cell clones isolated and maintained in culture

Apr 1987

CD8 coreceptor proven to be actively involved in antigen recognition by killer T cells

Jul 1987

Identification of the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)

Nov 1987

First evidence provided for the interaction between the surface molecule CD4 and major histocompatibility class II

12 Apr 1988

OncoMouse patent granted

May 1988 - Oct 1989

Cytotoxic T lymphocytes shown to recognise distinct surface markers on human melanoma

Jul 1988

Biochemical initiators of T Cell activitation, CD4 and CD8-p56, discovered

1988 - 1989

First evidence discovered of a physical link between oncoproteins and tumour suppressors

Dec 1988

Scientists report cloning the gene for the human cytotoxic T lymphocyte-associated antigen (CTLA-4)

1989

p53 demonstrated to be a tumour suppressor gene

1989

Mutations in p53 found in germline of cancer-prone families

Feb 1989

Scientists demonstrate the importance of CD28, a cell surface molecule found on T-cells, for the activation and survival of T cells

Sep 1989

Giorgio Trinchieri and colleagues identified interleukin-12 (IL-12), a cytokine that helps regulate the body’s resistance to infections and cancer

Sep 1989

DNA methylation suggested to inactivate tumour suppressor genes

Dec 1989

First use of genetically engineered T cells to redirect T cells to recognise and attack tumour cells

7 Dec 1989

Mutations in p53 gene found to play role in development of many common cancers

1990

US FDA approved BCG, a bacterial vaccine against tuberculosis, to treat early stage bladder cancer. It was the first FDA approved immunotherapy

Aug 1990

p53 found to arrest cell cyle

Aug 1990

BRCA1 gene linked with inherited predisposition to cancer

1991

p53 found to induce apoptosis, self destruction of a cell

1992

MDM2, an oncogene product, found to negatively regulate p53

1992

Mice genetically modified to be deficient in p53 shown to be prone to cancer

1 Oct 1992

First experimental evidence showing links between diet and DNA methylation and its relationship with cancer

1993

Wistar Institute patented Bcl-2, the first of a family of genes associated with different types of cancer

15 Apr 1993

Immune molecule, granulocyte-macrophage colony stimulating factor or GM-CSF, discovered to strengthen immunity against tumours

Sep 1993

p21 shown to be a p53 target gene

9 Feb 1994

Howard M Temin died

1994 - 1995

Identification and characterisation of the natural killer T cell, a lymphocyte able to bind and kill certain tumour and virus-infected cells

Jul 1994

DNA structure of p53-DNA elucidated

21 Apr 1995

First evidence published to demonstrate reduced DNA methylation contributes to formation of tumours

1 Feb 1996

Paper published indicating thymus-leukaemia antigen, a cell-surface marker, stimulates T cells to destroy specific target cells

22 Mar 1996

Mice experiments published demonstrating that blocking the CTLA-4 molecule on immune cells can cure cancer

Nov 1996

Experiments demostrate antigen-specific CD4+ and T cells become tolerant during tumour growth in test tubes

12 Jan 1997

Charles B Huggins died

Mar 1997

p53 shown to be linked to senescence, biological aging

29 Mar 1997

Ruth Sager died

1998

FDA approved Trastuzumab (Herceptin) for the treatment of metastatic breast cancer

20 Jul 1999

DNA methylation of CpG islands shown to be linked to colorectal cancer

2000

First clinical trials launched to test first immune checkpoint inhibitor drug containing a monoclonal antibody against CTLA-4 (ipilimumab, Yervoy®)

14 Sep 2002

Regulatory T cells discovered to restrain cytolytic T cells attacking cancer via messanger chemical called TGF-beta

17 Sep 2002

Cancer cells shown to be capable of hijacking PD-1 protein to evade destruction by immune system

1 Jan 2003

Sharma received ASCO Young Investigator Award to carry out clinical trials with NY-ES0-1 cancer vaccine

19 Mar 2003

Mutant mouse discovered capable of warding off aggressive cancer and its offspring found to confer resistance to cancer in 40% of his offspring

13 Dec 2003

Sharma discovered some bladder cancer cells expressed the marker NY-ESO-1 providing means for cancer vaccine

Dec 2005

p53 found to have antioxidant function

28 Mar 2006

Normal mice shown to become resistant to cancer when injected with white blood cells taken from mutant mice known to ward off aggressive cancer.

6 Oct 2006

FDA approved first histone deacetylase inhibitor, Vorinostat (Zolinza), for cutaneous T-cell lymphoma

15 Nov 2006

New enzyme identified as suppressor of p53 protein, a key molecule for controlling cancer in humans

2007

p53-induced senescence shown to prevent cancer

20 Sep 2007

Experiments in mice indicate cancer-killing capacity of granulocytes, white blood cells taken from humans

13 Nov 2007

Inappropriate activation of telomerase, an enzyme, shown to be associated with uncontrollable proliferation of cells seen in human cancers

10 Jun 2009

Stem cell transplants reported to improve survival for leukaemia patients

Nov 2009

FDA approved second histone deactylase inhibitor, Romidepsin (Istodax), for cutaneous T-cell lymphoma

25 Mar 2011

First immune checkpoint inhibitor drug targeting CTLA4 (ipilimumab, Yervoy®), approved by the FDA

19 Feb 2012

Renato Dulbecco died

Apr 2012

First child with leukaemia treated with adoptive cell therapy (CAR-T therapy)

2012

European approval of decatabine (Dacogen) for treatment of acute myeloid leukaemia

Sep 2014

FDA approved nivolumab (Opdivo®), an immune checkpoint inhibitor targeting PD1, for treating melanoma

22 Dec 2014

First immune checkpoint inhibitor drug targeting PD-1 approved in US

Apr 2015

Chinese regulatory authorities approved Chidamide, a histone deactylase inhibitor, for peripheral T cell lymphoma

3 Jun 2015

Irwin Rose died

5 Jun 2015

Two immunotherapy drugs reported to stop cancer cells avoiding destruction by immune system

27 Aug 2015

Experiments with mice showed that azacytidine treatment enhanced the responsiveness of tumors to anti–CTLA-4 therapy

27 Nov 2015

Experiments in mice indicate that a tumour's response to cancer immunotherapy using CTLA-4 checkpoint inhibitor can be improved by changing the gut microbiome

25 Mar 2016

Common tags discovered on the surface of cancer cells opening up new avenues for immunotherapy

15 Apr 2016

Gene editing used to prompt immune cells to combat cancer

1 May 2016

FDA approved atezolizumab (Tecentriq®), an immune checkpoint inhibitor targeted at PD1, for the treatment of urothelial carcinoma, the most common form of bladder cancer

Aug 2016

Marker identified for myeloid-derived suppressor cells, a type of cell associated with tumour resistance to certain cancer treatments

24 Oct 2016

FDA approved pembrolizumab (Keytruda®) for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 as determined by an FDA-approved test.

24 Feb 2017

Researchers report patients with greater diversity of gut bacteria have better response to cancer immunotherapy

23 Mar 2017

FDA granted accelerated approval to avelumab, a PD-L1 checkpoint inhibitor, to treat Merkel cell carcinoma, a rare form of skin cancer treatment, in patients 12 years and older with metastatic Merkel cell carcinoma, a rare form of skin disorder

12 Jul 2017

US FDA Oncologic Drugs Advisory Committee recommended the approval of the first adoptive cell therapy (CAR-T cell therapy) for B cell acute leukaemia

30 Aug 2017

USA FDA approved CAR-T therapy for certain pediatric and young adult patients with a form of acute lymphoblastic leukemia

2 Nov 2017

Cancer patients taking routine antibiotics before or soon after given PD-1 checkpoint inhibitor found to relapse quicker and have shorter survival time

2 Nov 2017

Experiments with mice show tumour growth can be reduced by giving faecal transplants from patients who positively responded to cancer immunotherapy

3 Nov 2017

Research showed simple blood test can identify patients at most risk of skin cancer returning

17 Jan 2018

Blood test detecting mutated DNA and proteins released by tumours shown to pick up early signs of 8 common cancers

1 Oct 2018

James Allison and Tasuku Honjo were awarded the Nobel Prize in Physiology or Medicine for their discovery of immune checkpoint inhibitors for cancer therapy