Cancer Biology

Proposed and confirmed important concepts about metastasis (that it is a non-random process) and tumor composition (that cells within a tumor have diverse properties and that not all cancer cells have the capacity to spread).

Fidler IJ. Selection of successive tumor lines for metastasis. Nature (New Biol). 1973;242(118):148-149.

Fidler IJ, Kripke ML. Metastasis results from preexisting variant cells within a malignant tumor. Science. 1977;197(4306):893-895.

Talmadge JE, Wolman SR, Fidler IJ. Evidence for the clonal origin of spontaneous metastases. Science. 1982;217(4557):361-363.

Demonstrated that both the growth and metastasis of cancer cells depend in part on molecules provided by normal cells and other aspects of the microenvironment surrounding a cancer, suggesting a new approach to therapy that targets normal cells.

Hart IR, Fidler IJ. Role of organ selectivity in the determination of metastatic patterns of the B16 melanoma. Cancer Res. 1980;40(7):2281-2287.

Fidler IJ, Hart IR. Biological diversity in metastatic neoplasms: origins and implications. Science. 1982;217(4564):998-1003.

Fidler IJ. The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer. 2003;3(6):453-458.

Designed models of human cancers in which human cancer cells are grown in athymic mice in the organ from which the cancer was derived; these models are especially useful for studying new therapies for human cancers.

Fidler IJ. Biology of cancer metastasis. In: Abeloff MD, Armitage JO, Niederhuber JE, Kastan MB, McKenna WG, eds. Clinical Oncology. 3rd ed. Philadelphia, PA: Elsevier Science; 2004:59-79.

Demonstrated in rats that a short exposure to environmental chemicals during development reprograms genes to become hyper-responsive to estrogen later in life, leading to a near-doubling in the incidence of uterine tumors in adult females.

Cook JD, Davis BJ, Cai SL, Barrett JC, Conti CJ, Walker CL. Interaction between genetic susceptibility and early-life environmental exposure determines tumor-suppressor-gene penetrance. Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8644-9.

Walker CL, Stewart EA. Uterine fibroids: the elephant in the room. Science. 2005 Jun 10;308(5728):1589-92.

Developed a mouse model that mimics human psoriasis and showed that the protein STAT3 must be present to initiate the disease. If new treatments can be developed to block the action of STAT3 in the human disease, this may open the door to more effective therapy.

Sano S, Chan KS, Carbajal S, Clifford J, Peavey M, Kiguchi K, Itami S, Nickoloff BJ, DiGiovanni J. Stat3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model. Nature Medicine. 2005 Jan;11(1):43-9.

First to demonstrate that VEGF may be a target for therapy in patients with colorectal cancer. Anti-VEGF therapy is now standard of care for patients with metastatic colorectal cancer.

Takahashi Y, Kitadai Y, Bucana C, Cleary KR, Ellis LM. Expression of vascular endothelial growth factor and its receptor (KDR) correlates with vascularity, metastasis and proliferation of human colon cancer. Cancer Res, 55:3964-3968,1995.

Identified the role of the cannabinoid receptor, CB1, as a tumor-suppressor in human colorectal cancer.

Wang D, Wang H, Ning W, Backlund MF, Dey SK, DuBois RN. Loss of cannabinoid receptor 1 accelerates intestinal tumor growth. Cancer Res. 2008;68(15) 6468-6476.

First demonstration that tumors stimulate specific types of bone marrow cells to migrate into the tumor.  These bone marrow cells help in the formation and expansion of the tumor vessels that bring oxygen and nutrients required for tumor growth. These bone marrow cells can help the tumor recover after anti-vascular therapy and may explain why tumors rebound after avastin (anti-VEGF) therapy.

Reddy K, Zhou Z, Jiao SF, Kleinerman ES. Specific bone marrow subsets differentiate into endothelial cells and pericytes and contribute to tumor vessel formation in Ewing’s sarcoma. Mol Cancer Res. 2008;6:929-936.

Showed that Jak2, a human tyrosine kinase that is activated in chronic myeloid leukemia (CML) cells, regulates several critical pathways that cause CML. In another myeloid leukemia, demonstrated that inhibition of Jak2 causes death of leukemia cells, leading to marked and durable benefits in patients with myelofibrosis. 

Samanta A, Perazzona B, Chakraborty S, Sun X, Modi H, Bhatia R, Priebe W, Arlinghaus R. Janus kinase 2 regulates Bcr-Abl signaling in chronic myeloid leukemia. Leukemia 2011;25(3):463-472.

Verstovsek S, Kantarjian H, Mesa RA, Pardanani AD, Cortes-Franco J, Thomas DA, Estrov Z, Fridman JS, Bradley EC, Erickson-Viitanen S, Vaddi K, Levy R, Tefferi A. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med 2010;363:1117-1127.