[Farnesyl transferase inhibitors--a novel agent for breast cancer].
The ras family of proto-oncogenes are upstream mediators of several essential cellular signal transduction pathways involved in cell proliferation and survival. Point mutations of ras oncogenes result in constitutive activation of oncogenic Ras. The key step in post-translational processing of Ras protein is farnesylation by farnesyl transferase. Inhibitors of this enzyme were developed initially as a therapeutic strategy for Ras-mutated tumors. Moreover, it is now clear that farnesyl transferase inhibitors (FTIs) have activity independent of Ras, and show some effects on tumors without oncogenic ras mutations. Preclinical data show that FTIs can inhibit proliferation of breast cancer cells in vitro and in vivo, and phase II studies of FTI-R115777 in advanced breast cancer show encouraging results. Therefore, FTIs, used alone or with other agents, may be a novel therapeutic approach for breast cancer.
Zhang
Ming
M
Department of Medical Oncology, The Fourth Affiliated Hospital, Hebei Medical University, Shijiazhuang, Hebei 050011, P. R. China.
Jiang
Da
D
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors*; D005260:Female; D011905:Genes, ras; D006801:Humans; D010880:Piperidines / Q000627:therapeutic use; D017368:Protein Prenylation; D011725:Pyridines / Q000627:therapeutic use; D015363:Quinolones / Q000627:therapeutic use; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism; D003986:Dibenzocycloheptenes
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D051231:Farnesyltranstransferase; D010880:Piperidines; D011725:Pyridines; D015363:Quinolones; D018631:ras Proteins; C115354:lonafarnib; D003986:Dibenzocycloheptenes; C402769:tipifarnib