Multilevel modulation of the mevalonate and protein-prenylation circuitries as a novel strategy for anticancer therapy.
The important role of the mevalonate and protein-prenylation circuitries in the process of carcinogenesis is increasingly being recognized. Accordingly, several enzymes within these pathways have been pharmacologically targeted for anticancer drug development. Despite promising activity in a plethora of preclinical models, clinical evaluation of these agents as monotherapy against various malignancies has been disappointing. Appropriate combinations of inhibitors of isoprenoid biosynthesis, inhibitors of prenylation and postprenylation modifications might be a more clinically effective strategy for anticancer therapy.
Konstantinopoulos
Panagiotis A
PA
Department of Biological Chemistry, Medical School, University of Athens, 11527 Athens, Greece.
Papavassiliou
Athanasios G
AG
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008798:Mevalonic Acid / Q000037:antagonists & inhibitors*; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017368:Protein Prenylation / Q000187:drug effects*
D004791:Enzyme Inhibitors; D008798:Mevalonic Acid