24 Milestones in Cancer: LICR Investigators Pivotal in Five
The Nature Publishing Group has given its opinion on the ‘24 Milestones in Cancer Research’ since the end of the nineteenth century. ‘Original Research Papers’ authored by LICR investigators feature in five of the 24 Milestones, with another two quoting papers authored by LICR investigators as selected ‘Further Reading.’ That’s about 30% of cancer research milestones with significant contributions from LICR investigators according to the editors of Nature, Nature Medicine and Nature Reviews Cancer.
- MILESTONE #3: Drs. Thierry Boon (Director, Brussels Branch) and Aline Van Pel (Brussels Branch) for discovering that specific immunity to spontaneous tumors could be induced by vaccinating mice with mutagenized tumor cells(1), and then Drs. Boon and Pierre Van Der Bruggen (Brussels Branch) and Dr. Alex Knuth (Affiliate, Zurich) for identifying the first tumor-specific antigen, MAGE, recognized by cytolytic T cells in humans(2). Dr. Lloyd Old (Director, New York Branch) is a co-author of the referenced immunosurveillance studies(3);
- MILESTONE #11: Dr. Webster Cavenee (Director, San Diego Branch) for localizing the retinoblastoma (RB) gene and showing that inherited and sporadic cancers had homozygosity for mutations at the RB region, thereby confirming the allelic-hit hypothesis(4);
- MILESTONE #16: Drs. Michael Waterfield (former Director, UCL Branch) and Carl-Henrik Heldin (Director, Uppsala Branch) identifying the transforming simian sarcoma virus protein as platelet-derived growth factor (PDGF)(5), and then Dr. Waterfield, together with Dr. Yossi Schlessinger (LICR Affiliate, New Haven), identifying the transforming protein from the avian erythroblastosis virus as epidermal growth factor receptor (EGFR)(6);
- MILESTONE #20: Role of RB and p53 in cell-cycle and DNA-damage
checkpoints
* A paper from Dr. Lloyd Old (Director, New York Branch) is suggested as Further Reading(7); - MILESTONE #21: The genetic bases of cancer-predisposition syndromes
* Papers from Drs. Webster Cavenee(8) and Richard D. Kolodner (LICR Executive Director for Laboratory Sciences & Technology, and San Diego Branch)(9,10) are suggested as Further Reading; - MILESTONE #22: Dr. Richard D. Kolodner for the identification of the human mismatch repair gene MutS in hereditary non-polyposis colon cancer as part of the work that established DNA repair defects affect, or are necessary, for cancer development(9,10);
- MILESTONE #24: Dr. George Demetri (Executive Director for Clinical & Translational Sciences) was the first to show that non-promiscuous inhibitor could selectively target tumors, in this case Glivec targeting treat advanced gastrointestinal stomach tumors(11).
References
- Van Pel A. and Boon T. Protection against a nonimmunogenic mouse leukemia by an immunogenic variant obtained by mutagenesis. Proc Natl.Acad.Sci.U.S.A (1982) 79(15):4718-4722.
- van der Bruggen P., Traversari C., Chomez P., Lurquin C., De Plaen E., Van den E.B., Knuth A., and Boon T. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science (1991) 254(5038):1643-1647.
- Shankaran V., Ikeda H., Bruce A.T., White J.M., Swanson P.E., Old L.J., and Schreiber R.D. IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature (2001) 410(6832):1107-1111.[PMID: ]
- Cavenee W.K., Dryja T.P., Phillips R.A., Benedict W.F., Godbout R., Gallie B.L., Murphree A.L., Strong L.C., and White R.L. Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. Nature (1983) 305(5937):779-784.
- Waterfield M.D., Scrace G.T., Whittle N., Stroobant P., Johnsson A., Wasteson A., Westermark B., Heldin C.H., Huang J.S., and Deuel T.F. Platelet-derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus. Nature (1983) 304(5921):35-39
- Downward J., Yarden Y., Mayes E., Scrace G., Totty N., Stockwell P., Ullrich A., Schlessinger J., and Waterfield M.D. Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature (1984) 307(5951):521-527.
- DeLeo A.B., Jay G., Appella E., DuBois G.C., Law L.W., and Old L.J. Detection of a transformation-related antigen in chemically induced sarcomas and other transformed cells of the mouse. Proc.Natl.Acad.Sci.U.S.A (1979) 76(5):2420-2424.
- Gessler M., Poustka A., Cavenee W., Neve R.L., Orkin S.H., and Bruns G.A. Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping. Nature (1990) 343(6260):774-778.
- Bronner C.E., Baker S.M., Morrison P.T., Warren G., Smith L.G., Lescoe M.K., Kane M., Earabino C., Lipford J., Lindblom A., Tannergard P., Bollag R.J., Godwin A.R., Nordenskjosolld M., Fishel R., Kolodner R., and Liskay R.M. Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature (1994) 368(6468):258-261.
- Fishel R., Lescoe M.K., Rao M.R., Copeland N.G., Jenkins N.A., Garber J., Kane M., and Kolodner R. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell (1993) 75(5):1027-1038.
- Demetri G.D., von Mehren M., Blanke C.D., Van den Abbeele A.D., Eisenberg B., Roberts P.J., Heinrich M.C., Tuveson D.A., Singer S., Janicek M., Fletcher J.A., Silverman S.G., Silberman S.L., Capdeville R., Kiese B., Peng B., Dimitrijevic S., Druker B.J., Corless C., Fletcher C.D., and Joensuu H. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N.Engl.J.Med. (2002) 347(7):472-480.