title: Mutant onco-proteins as drug targets: successes, failures, and future prospects.
abstract: Mutant onco-proteins play a direct, causal role in cancer and are therefore considered attractive drug targets. Clinical experience has supported this view, with some exceptions. However, clinical benefit has often been restricted by rapid emergence of drug-resistant clones through several distinct mechanisms. This problem can, in principle, be addressed through cocktails containing several drugs. However, the number of tumors whose survival is dependent on a single, druggable mutant onco-protein is currently unknown. The majority of tumors may be driven either by single drivers that are un-druggable, or by combinations of drivers. In both cases, new approaches will be necessary. Development of systemic RNA interference may be a solution to these problems.
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, UCSF, 1450 3rd Street, Room 371, Box 0128, San Francisco, CA 94158, USA. mccormick@cc.ucsf.edu
authors.forename: Frank
authors.initials: F
authors.lastname: McCormick
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015195:Drug Design; D006801:Humans; D050505:Mutant Proteins / Q000235:genetics*; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D050505:Mutant Proteins