SRC family nonreceptor tyrosine kinases as molecular targets for cancer therapy.
The Src family of kinases has nine known members, all of which are nonreceptor tyrosine kinases involved in signal transduction in both normal and cancer cells. Interest in these kinases has increased recently because of the development, initial clinical success, and low toxicity of pharmacologic inhibitors. c-Src is the best-studied member of the Src family and the one most often implicated in cancer progression. c-Src has multiple substrates that lead to diverse biologic effects, including changes in proliferation, motility, invasion, survival, and angiogenesis. c-Src has been most extensively studied in colon cancer where correlative and direct experimental evidence has shown that it mediates several aspects of cancer cell progression. c-Src has a similar role in multiple tumor types, including pancreatic cancer, breast cancer, lung cancer, head and neck squamous cell carcinoma, and prostate cancer. Several inhibitors of the Src family kinases are in clinical development; three are currently being studied in clinical trials. Initial data from these trials suggest that these agents are well tolerated. Future clinical development of these inhibitors will include trials in patients with solid tumors and of combination therapy.
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. fmjohns@mdanderson.org
Faye M
FM
Johnson
Gary E
GE
Gallick
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D007155:Immunologic Factors / Q000737:chemistry* / Q000494:pharmacology; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology
D000970:Antineoplastic Agents; D007155:Immunologic Factors; D019061:src-Family Kinases