New targets for therapy in breast cancer: Farnesyltransferase inhibitors

摘要: Current systemic therapies for breast cancer are often limited by their nonspecific mechanism of action, unwanted toxicities on normal tissues, and short-term efficacy due to the emergence drug resistance. However, identification molecular abnormalities in cancer, particular key proteins involved abnormal cell growth, has resulted development various signal transduction inhibitor drugs as new treatment strategies against disease. Protein farnesyltransferase inhibitors (FTIs) were originally designed target Ras pathway, although it is now clear that several other intracellular dependent post-translational farnesylation function. Preclinical data revealed FTIs inhibit growth ras-transformed cells, they also potent a wide range lines contain wild-type ras, including cells. Additive or synergistic effects observed when combined with cytotoxic agents (in taxanes) endocrine (tamoxifen). Phase I trials have explored different schedules prolonged administration, dose-limiting included myelosuppression, gastrointestinal toxicity neuropathy. Clinical was seen FTI tipifarnib phase II study. Based promising preclinical suggest synergy taxanes therapy, combination clinical studies progress determine whether can add further conventional therapies.