Oncology

Oncology: timeline of key events

Date	Event	People	Places
23 Apr 1867	Johannes A G Fibiger was born in Silkeborg, Denmark	Fibiger	Silkeborg, Denmark
5 Oct 1879	Francis Peyton Rous was born in Baltimore MD, USA	Rous	Rockefeller University
May 1893	First successful treatment of cancer patient with immunotherapy	Coley	Memorial Sloan Kettering Cancer Center
1895	Humans treated with antiserum prepared against human cancer. This established the principle of using serotherapy to fight cancer	Hericourt, Richet	College de France
1899	First commercial vaccine developed for treatment of sarcoma	Coley	Memorial Sloan Kettering Cancer Center, Parke Davis & Co
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	Leob, Jensen	University of Pennsylvania, Agriculture and Veterinary Institute
22 Sep 1901	Charles B Huggins was born Halifax, Canada	Huggins	University of Chicago
1902	First attempt to vaccinate against cancer with a patient's own tumour tissue	von Leyden, Blumenthal
1910	Austrian physicians Ernest Freund and Gisa Kaminer observed that something in blood serum from cancer patients pervents the destruction of cancer cells	Freund, Kaminer	Rudolf-Stiftung Hospital
1911	First cancer-causing virus discovered	Rous	Rockefeller University
1914	Experiments by James B Murphy demonstrate that lymphocytes help animals reject grafted tumours	Murphy	Rockefeller Intitute
22 Feb 1914	Renato Dulbecco was born in Catanzaro, Italy	Dulbecco	Imperial 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 mice	Murphy, Morton	Rockefeller Institute
19 Sep 1915	Elizabeth Stern was born in Cobalt, Ontario, Canada	Stern	University of California at Los Angeles
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.	Murphy	Rockefeller Institute
7 Feb 1918	Ruth Sager was born in Brookline, Massachusetts, USA	Sager	Rockefeller University
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.	Freund, Kaminer	Rudolf-Stiftung Hospital
30 Jan 1928	Johannes Fibiger died	Fiber
16 Dec 1928	Bruce N Ames was born in New York, USA	Ames	University of California Berkeley
1929	First molecular marker, antigen, identified on a tumour, laying foundation for use of antibodies to diagnose and treat cancer	Witebsky	University of Heidelberg
1929	Jackson Memorial Laboratories established to develop inbred strains of mice to study the genetics of cancer and other diseases		Jackson Memorial Laboratoroies
April 1929	Autopsies carried out on tuberculosis patients show them less likely to have contracted cancer	Pearl	Johns Hopkins University
23 Jan 1930	Beverly Griffin was born in Delhi, Louisiana, USA	Griffin	Imperial College
10 Dec 1934	Howard M Temin was born in Philadelphia, PA, USA	Temin	University of Wisconsin
22 Feb 1936	John Michael Bishop born in York, PA, USA	Bishop	University California San Francisco
7 Mar 1938	David Baltimore was born in New York City	Baltimore	New York City
18 Dec 1939	Harold E Varmus was born in Oceanside NY, USA	Varmus	University of California San Francisco
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	Barrett	Jackson Memorial Laboratoroies
6 Dec 1941	Ronald Levy was born in Carmel, California, United States	Levy	Stanford University
25 Jan 1949	Paul M Nurse was born in Norwich, United Kingdom	Nurse	Imperial Cancer Research Fund, Francis Crick Institute
1953	FDA approved 6-mercaptopurine as treatment for childhood leukaemia	Elion, Hitching	Wellcome Research Laboratories
1957 - 1959	Concept developed that the immune system naturally protects against cancer	Burnet, Lewis
1957	Leukaemia virus found, reinforcing idea that viruses can cause cancer	Friend	Memorial Sloan Kettering Cancer Center
1959	Bone marrow transplants in two sets of identical twin girls fails to eradicate leukaemia	Thomas, Ferrebee, Sahler	Bassett Medical Center
25 Jul 1959	First direct evidence of the immune system's ability to prevent cancer provided by Lloyd Old and colleagues	Old, Clarke, Benacerraf	Memorial Sloan Kettering Cancer Center
December 1961	Normal cell population discovered to only be able to divide a limited number of times before it stops	Hayflick	Wistar Institute
1963	First report linking a specific virus (herpes simplex virus) to a specific cancer (cervical cancer)	Stern	University of California, Los Angeles
December 1966	Scientists detect antibodies to the Epstein-Barr virus in patients with nasopharyngeal cancer which suggest the cancer is caused by a virus.	Old, Boyse, Oettgen	Memorial Sloan Kettering Cancer Center
February 1969	Team led by Karl and Ingegerd Hellstrom observe serum from mice with chemically induced tumours can block reaction of lymphocytes	Hellstrom, Evans, Heppner, Pierce, Yang	Fred Hutchinson Cancer Center
7 Nov 1969	Fluorescence activated cell sorter (FACS) published	Herzenberg, Hulett, Bonner, Barrett	Stanford University
1 Dec 1970	First oncogene (SRC gene) discovered in a virus	Duesberg, Vogt	University of California San Francisco
June 1971	Hellstom team suggest that antibodies bound to tumour cells mask their detection by the immune system	Sjogren, Hellstrom, Bansal	Fred Hutchinson Cancer Center
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		Wistar Institute
16 Feb 1972	Francis Peyton Rous died	Rous	Rockefeller University
1973	First successful bone marrow transplant from unrelated donor	Good, O'Reilly	Memorial Sloan Kettering Cancer Center
1 Mar 1973	Ames test developed that identifies chemicals that damage DNA	Ames, Lee, Durston	University of California Berkeley
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	Stutman	Memorial Sloan-Kettering Cancer Center
February 1975	Natural killer cell identified in mice and shown to be important part of immune system	Kiessling, Klein, Pross, Wigzell	Karolinska Institute
15 Apr 1975	Human natural killer cell isolated	Jondal, Pross	Karolinska Institute
24 Apr 1975	Discovery of unique molecular marker, idiotype, on blood cancer cells, opening new avenue for cancer diagnosis and therapy	Stevenson	Tenovus Research Laboratory
25 Apr 1975	Unique 'idiotype' marker discovered on the surface of proteins in cancer cells, providing target for treating cancer with antibodies	Stevenson	Southampton University
September 1975	Tumour necrosis factor (TNF) was discovered. It was the first immune molecule shown to kill cancer cells	Carswell, Old, Kassel, S.Green, Fiore, Williamson	Memorial Sloan Kettering Cancer Center
11 Mar 1976	Proto-oncogenes suggested to be part of the genetic machinery of normal cells and play important function in the developing cell	Bishop, Varmus, Stehelin, Vogt	University of California San Francisco
10 Sep 1976	Discovery of first T cell growth factor, later named Interleukin-2 (IL-2)	Morgan, Ruscetti, Gallo	Litton Bioethics Research Laboratories, National Cancer Institute
February 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	Robinson, Owen	University of Newcastle upon Tyne
1 Apr 1977	Development of first anti-idiotype antibodies. These are shown to activate immune defense cells to attack tumour cells in guinea-pigs	Stevenson, Elliott	Tenovus Research Laboratory
July 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	Ruscetti, Morgan, Gallo	National Cancer Institute
1978	T cell-mediated immunity shown to aid tumour regression	Berendt, North, Kirstein	Trudeau Institute
1979	The first tumour suppressor gene was discovered, known as p53	Crawford, Lane, Deleo, Old, Levine
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	Stern	University of California at Los Angeles
10 Jul 1981	Complete library of overlapping DNA fragments of Epstein Barr Virus cloned	Griffin, Arrand, Walsh, Bjorck, Rymo	Imperial Cancer Research Fund Laboratories, University of Gothenberg
1982	Azacitidine fails to win FDA approval for treatment of acute myelogenous leukaemia due to lack of controlled studies showing clinical benefit
June 1982	Steven Rosenberg and colleagues first describe lymphokine-activated killer cells	Grimm, Mazumder, Zhang, Rosenberg	National Cancer Institute
November 1982	James Allison and collegues use monoclonal antibody to provide first biochemical description of tumour specific antigen of murine T-lymphoma	Allison, McIntyre, Bloch	University of Texas System Cancer Center
1 Dec 1982	First molecular markers, antigens, identified in melanoma tumours. These markers are now targeted by cancer drugs	Houghton, Eisinger, Albino, Cairncross, Old	Memorial Sloan Kettering Cancer Center
1983	Link drawn between immune deficiency and cancer		Memorial Sloan Kettering Cancer Center
1983	Murine p53 gene cloned	Levine, Oren	Weizmann Institute, State University New York
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	Bosma, Custer	Fox Chase Cancer Center
24 Mar 1983	First cloning of Interleukin 2 (Il-2)	Taniguchi, Matsui, Fujita, Takaoka, Kashmina, Yoshimoto, Hamuro	Japanese Foundation for Cancer Research, Ajinomoto Co Inc
June 1983	Harald Zur Hausen identifies the human papillomavirus as the causative agent of cervical cancer	zur Hausen	University of Freiberg
November 1983	A team of researchers including Philippa Marrack, John Kappler and James P Allison identified the first T cell antigen receptor	Kappler, Kubo, Haskins, Hannum, Marrack, Pigeon, McIntyre, Allison, Trowbridge	University of Colorado, University of Texas System Cancer Center, National Jewish Hospital and Research Cener, Salk Institute
1984	p53 inactivated in tumour cells for first time	Wolf, Rotter	Weizmann Institute
1984	Human p53 gene cloned	Matlashewski, Lamb, Pim, Peacock, Crawford, Benchimo	Imperial Cancer Research Fund Laboratories, Ontario Cancer Institute, University of Toronto
June 1984	First clinical experiments demonstrate the possibility of training T cells to attack tumours	Knuth, Danowski, Oettgen, Old	Memorial Sloan-Kettering Cancer Center
1985	T cell surface proteins CD4 and CD8 cloned	Maddon, Littman, Godfrey, Maddon Chess, Axel	Columbia University
December 1985	IL-2 based immunotherapy shown to reduce tumours in patients with melanoma and renal cell cancer	Rosenberg	National Cancer Institute
12 Dec 1985	New transgenic mouse model announced for studying cancer	Adams, Harris, Pinkert, Corcoran, Alexander, Cory, Palmiter, Brinster	Walter and Eliza Hall Institute, University of Pennsylvania, Howard Hughes Medical Institute
December 1986	Anti-tumour responses observed in 3 out of 10 patients given high-doses of Interleukin-2 (IL-2)	Rosenberg, Lotze, Chang, Seipp, Simpson, Vetto	National Cancer Institute
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	De Plaen, Boon	Ludwig Institute for Cancer Research
15 Mar 1987	First stable human anti-tumour cytotoxic T cell clones isolated and maintained in culture	Herin, Lemoine, Weynants, Vessiere, Van Pel, Knuth, Devos, Boon	Ludwig Institute
April 1987	CD8 coreceptor proven to be actively involved in antigen recognition by killer T cells	Dembic, Haas, Zamoyska, Parnes, Steinmetz, von Boehmer	Basel Institute of Immunology
July 1987	Identification of the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)	Brunet, Denizot, Luciani, Roux-Dosseto, Suzan, Mattei, Golstein	INSERM-CNRS
November 1987	First evidence provided for the interaction between the surface molecule CD4 and major histocompatibility class II	Doyle, Strominger	Harvard University
12 Apr 1988	OncoMouse patent granted	Leder, Stewart	Harvard University
May 1988 - Oct 1989	Cytotoxic T lymphocytes shown to recognise distinct surface markers on human melanoma	Wolfel, Knuth, Degiovanni, Van den Eynde, Hainaut, Boon	Ludwig Institute for Cancer Research
July 1988	Biochemical initiators of T Cell activitation, CD4 and CD8-p56, discovered	Rudd, Trevillyan, Dasupta, Wong, Schlossman	Dana-Faber Cancer Institute, Harvard University, Tech University
1988 - 1989	First evidence discovered of a physical link between oncoproteins and tumour suppressors
December 1988	Scientists report cloning the gene for the human cytotoxic T lymphocyte-associated antigen (CTLA-4)	Dariavach, Mattei, Golstein, Lefranc	INSERM-CNRS
1989	p53 demonstrated to be a tumour suppressor gene	Baker, 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
1989	Mutations in p53 found in germline of cancer-prone families	Malkin, Srivastava, Zou, Pirollo, Blattner, Chang	Massachusetts General Hospital, Uniformed Services University
February 1989	Scientists demonstrate the importance of CD28, a cell surface molecule found on T-cells, for the activation and survival of T cells	Thompson, Lindsten, Ledbetter, Kunkel, Young, Emerson, Leiden, June	Howard Hughes Medical Institute
September 1989	Giorgio Trinchieri and colleagues identified interleukin-12 (IL-12), a cytokine that helps regulate the body’s resistance to infections and cancer	Kobayashi, Fitz, Ryan, Hewick, Clark, Chan, Loudon, Sherman, Perussia, Trinchieri	Wistar Institute
September 1989	DNA methylation suggested to inactivate tumour suppressor genes	Greger, Passarge, Hopping, Messmer, Horsthemke	Institute of Human Genetics
December 1989	First use of genetically engineered T cells to redirect T cells to recognise and attack tumour cells	Gross, Waks, Eshhar	Weizmann Institute
7 Dec 1989	Mutations in p53 gene found to play role in development of many common cancers	Vogelstein, Nigro	Johns Hopkins University
1990	US FDA approved BCG, a bacterial vaccine against tuberculosis, to treat early stage bladder cancer. It was the first FDA approved immunotherapy	Herr, Oettgen	Memorial Sloan Kettering Cancer Center
August 1990	p53 found to arrest cell cyle	Michalovitz, Halevy, Oren, Mercer, Shields, Amin, Sauve, Appella, Romano, Ullrich	Weizmann Institute, Temple University
21 Dec 1990	BRCA1 gene linked with inherited predisposition to cancer	King	University of California Berkley
1991	p53 found to induce apoptosis, self destruction of a cell	Yonish-Rouach, Resnitzky, Lotem, Sachs, Kimchi, Oren	Weizmann Institute
1992	MDM2, an oncogene product, found to negatively regulate p53	Momand, Zambetti, Olson, George, Levine	Princeton University
1992	Mice genetically modified to be deficient in p53 shown to be prone to cancer	Donehower, Harvey, Slagle, McArthur, Montgomery, Butel, Bradley	Baylor College
1 Oct 1992	First experimental evidence showing links between diet and DNA methylation and its relationship with cancer	Zapisek, Cronin, Lyn-Cook, Poirier	FDA, National Center for Toxicological Research
1993	Wistar Institute patented Bcl-2, the first of a family of genes associated with different types of cancer		Wistar Institute
15 Apr 1993	Immune molecule, granulocyte-macrophage colony stimulating factor or GM-CSF, discovered to strengthen immunity against tumours	Dranoff, Jaffee, Lazenby, Golumbek, Levitsky, Brose, Jackson, Hamada, Pardoll, Mulligan	Massachusetts Institute of Technology
September 1993	p21 shown to be a p53 target gene	el-Deiry, Tokino, Velculescu, Levy, Parsons, Trent, Lin, Mercer, Kinzler, Vogelstein	Johns Hopkins University, National Center for Human Genome Research, Thomas Jefferson University
9 Feb 1994	Howard M Temin died	Temin	University of Wisconsin
1994 - 1995	Identification and characterisation of the natural killer T cell, a lymphocyte able to bind and kill certain tumour and virus-infected cells	Bendelac	University of Chicago
July 1994	DNA structure of p53-DNA elucidated	Cho, Gorina, Jeffrey, Pavletich	Memorial Sloan-Kettering Cancer Center
21 Apr 1995	First evidence published to demonstrate reduced DNA methylation contributes to formation of tumours	Laird, Jackson-Grusby, Fazeli, Dickinson, Jung, Li, Weinberg, Jaenisch	Massachusetts Institute of Technology, Massachusetts General Hospital
1 Feb 1996	Paper published indicating thymus-leukaemia antigen, a cell-surface marker, stimulates T cells to destroy specific target cells	Sharma	Pennsylvania State University
22 Mar 1996	Mice experiments published demonstrating that blocking the CTLA-4 molecule on immune cells can cure cancer	Leach, Krummel, Allison	University of California Berkeley
November 1996	Experiments demostrate antigen-specific CD4+ and T cells become tolerant during tumour growth in test tubes
12 Jan 1997	Charles B Huggins died	Huggins	University of Chicago
March 1997	p53 shown to be linked to senescence, biological aging	Serrano , Lin, McCurrach, Beach, Lowe	Cold Spring Harbor Laboratory
29 Mar 1997	Ruth Sager died	Sager	Rockefeller University
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	Toyota, Ahuja, Ohe-Toyota, Herman, Baylin, Issa	Johns Hopkins University
2000	First clinical trials launched to test first immune checkpoint inhibitor drug containing a monoclonal antibody against CTLA-4 (ipilimumab, Yervoy®)	Allison	Medarex, University of California Berkley
14 Sep 2002	Regulatory T cells discovered to restrain cytolytic T cells attacking cancer via messanger chemical called TGF-beta	Herlyn, Somasundaram	Wistar Institute
17 Sep 2002	Cancer cells shown to be capable of hijacking PD-1 protein to evade destruction by immune system	Iwai , Ishida, Tanaka, Okazaki, Honjo, Minato	Japan Science and Technology Corporation
1 Jan 2003	Sharma received ASCO Young Investigator Award to carry out clinical trials with NY-ES0-1 cancer vaccine	Sharma	Memorial Sloan-Kettering Cancer Center
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	Cui, Willingham, Hicks, Alexander-Miller, Howard, Hawkins, Millier, Weir, Du, DeLong	Wake Forest University
13 Dec 2003	Sharma discovered some bladder cancer cells expressed the marker NY-ESO-1 providing means for cancer vaccine	Sharma	Memorial Sloan-Kettering Cancer Center
December 2005	p53 found to have antioxidant function	Sablina, Budanov, Ilyinskaya, Agapova, Kravchenko, Chumakov	Lerner Research Institute
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.	Hicks, Redlinger, Willingham, Alexander-Miller, Kap-Herr, Pettenati, Sanders, Weir, Du, Kim, Simpson, Old, Cui	Wake Forest University, Ludwig Institute for Cancer Research
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	Berger	Wistar Institute, Vienna Biocenter
2007	p53-induced senescence shown to prevent cancer	Ventura, Kirsch, McLaughlin, Tuveson, Grimm, Lintault, Newman, Reczek, Weissleder, Jacks, Xue, Zender, Miething, Dickins, Hernando, Krizhanovsky, Cordon-Cardo, Lowe	Massachusetts Institute of Technology, Massachusetts General Hospital, Harvard University, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory
20 Sep 2007	Experiments in mice indicate cancer-killing capacity of granulocytes, white blood cells taken from humans	Cui	Wake Forest University
13 Nov 2007	Inappropriate activation of telomerase, an enzyme, shown to be associated with uncontrollable proliferation of cells seen in human cancers	Skordalakes	Wistar Institute
10 Jun 2009	Stem cell transplants reported to improve survival for leukaemia patients	Koreth, Schlen, Kopecky, Honda, Sierra, Djulbegovic, Wadleigh, DeAngelo, Stone, Sakamaki Appelbaum, Dohner, Antin, Soiffer, Cutler	Dana Farber Cancer Institute
November 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	Allison	Medarex, University of California Berkley
19 Feb 2012	Renato Dulbecco died	Dulbecco	Imperial Cancer Research Fund Laboratory
April 2012	First child with leukaemia treated with adoptive cell therapy (CAR-T therapy)	June, Whitehead	Children's Hospital of Philadelphia, University of Pennsylvania
2012	European approval of decatabine (Dacogen) for treatment of acute myeloid leukaemia
September 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	Honko, Freeman, Lonberg	Medarex, Bristol-Myers Squibb, Ono Pharmaceutical, Kyoto University
April 2015	Chinese regulatory authorities approved Chidamide, a histone deactylase inhibitor, for peripheral T cell lymphoma
3 Jun 2015	Irwin Rose died	Rose	University of California Irvine
5 Jun 2015	Two immunotherapy drugs reported to stop cancer cells avoiding destruction by immune system	Allison
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	Zitvogel, Veitzou,	Institut Gustave Roussy
25 Mar 2016	Common tags discovered on the surface of cancer cells opening up new avenues for immunotherapy	McGranahan, 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, Mergh	University 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 2016	Gene editing used to prompt immune cells to combat cancer	Quezada, Johnson, Menger, Sledzinska, Bergerhoff, Vargas, Smith, Poirot, Pule, Hererro, Peggs	University College London, Cancer Research UK, Cellectis
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		Genentech, Roche
13 Jun 2016	Beverly Griffin died	Griffin	Imperial College
August 2016	Marker identified for myeloid-derived suppressor cells, a type of cell associated with tumour resistance to certain cancer treatments		Wistar Institute
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.		Merck
24 Feb 2017	Researchers report patients with greater diversity of gut bacteria have better response to cancer immunotherapy	Wargo, Gopalakrishnan	MD Anderson Cancer Center
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		EMD Serono, Merck KGaA, Pfizer
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	June	Novartis, University of Pennsylvania
30 Aug 2017	USA FDA approved CAR-T therapy for certain pediatric and young adult patients with a form of acute lymphoblastic leukemia	June	Novartis, University of Pennsylvania
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	Zitvogel, Kroemer	Institut Gustave Roussy
2 Nov 2017	Experiments with mice show tumour growth can be reduced by giving faecal transplants from patients who positively responded to cancer immunotherapy	Wargo, Gopalakrishnan	MD Anderson Cancer Center, Institute Gustave-Roussy
3 Nov 2017	Research showed simple blood test can identify patients at most risk of skin cancer returning	Lee, Gremel, Marshall, Myers, Fisher, Dunn, Dhomen, Corrie, Middleton, Lorigan, Marais	University of Manchester
17 Jan 2018	Blood test detecting mutated DNA and proteins released by tumours shown to pick up early signs of 8 common cancers	Cohen, 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, Falc	Johns Hopkins University
12 Jul 2018	Genetic test shown to accurately predict which women benefit from chemotherapy	Sparano	Genomic Health
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	Allison, Honjo	University of Texas MD Anderson Cancer Center, Kyoto University
21 Dec 2018	CRISPR-Cas9 editing helped restore effectiveness of first-line chemotherapies for lung cancer	Kmiec, Bialk, Wang, Hanas	Helen F Graham Cancer Center and Research Institute

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

First cancer-causing virus discovered

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

23 Jan 1930

Beverly Griffin was born in Delhi, Louisiana, USA

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

25 Jan 1949

Paul M Nurse was born in Norwich, United Kingdom

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

Dec 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

7 Nov 1969

Fluorescence activated cell sorter (FACS) published

1 Dec 1970

First oncogene (SRC gene) discovered in a virus

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

1 Mar 1973

Ames test developed that identifies chemicals that damage DNA

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

11 Mar 1976

Proto-oncogenes suggested to be part of the genetic machinery of normal cells and play important function in the developing cell

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

21 Dec 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

13 Jun 2016

Beverly Griffin died

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

12 Jul 2018

Genetic test shown to accurately predict which women benefit from chemotherapy

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

21 Dec 2018

CRISPR-Cas9 editing helped restore effectiveness of first-line chemotherapies for lung cancer