Farnesyltransferase inhibitors in breast cancer therapy.
Farnesyltransferase inhibitors (FTIs) belong to a group of agents originally designed to prevent membrane attachment of Ras protein by inhibiting a key step in its post-translational processing. It was thus hypothesized that FTIs would curtail the oncogenic ras-mediated proliferative and antiapoptotic signals that are activated in human tumors. Although the Ras protein is mutated in only < 5% of breast cancers, there are multiple aberrant pathways that lead to activation of wild-type ras signaling. Moreover, FTIs have consistently demonstrated efficacy in tumors regardless of their ras mutational status. Thus, the role of other protein targets in mediating the antitumor effect of FTIs is being elucidated. This article reviews current data on the use of FTIs in breast cancer.
Dy
Grace K
GK
Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. adjei.alex@mayo.edu
Adjei
Alex A
AA
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors* / Q000502:physiology; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D000069287:Capecitabine; D002986:Clinical Trials as Topic; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D051231:Farnesyltranstransferase; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D017239:Paclitaxel / Q000008:administration & dosage; D010880:Piperidines / Q000008:administration & dosage; D017368:Protein Prenylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D011725:Pyridines / Q000008:administration & dosage; D015363:Quinolones / Q000008:administration & dosage; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D003986:Dibenzocycloheptenes
D019883:Alkyl and Aryl Transferases; D000069287:Capecitabine; D003841:Deoxycytidine; D004791:Enzyme Inhibitors; D051231:Farnesyltranstransferase; D005472:Fluorouracil; D009363:Neoplasm Proteins; D017239:Paclitaxel; D010880:Piperidines; D011725:Pyridines; D015363:Quinolones; C115354:lonafarnib; D003986:Dibenzocycloheptenes; C402769:tipifarnib