title: Survivin in solid tumors: rationale for development of inhibitors.
abstract: Survivin is a 16.5 kDa protein that functions to inhibit apoptosis, promote proliferation, and enhance invasion. Absent in most adult tissues, survivin is selectively upregulated in many human tumors, where its overexpression correlates with poor outcome and treatment resistance. Consequently, survivin is a promising target for cancer therapy. Preclinical data demonstrate that survivin inhibition reduces cell proliferation, increases apoptosis, and sensitises cells to cytotoxic agents and radiotherapy. The pharmacological survivin inhibitors LY2181308 and YM155 have demonstrated acceptable toxicity and evidence of therapeutic efficacy as single agents in early-phase clinical trials. Current efforts seek to define the optimum use of survivin inhibitors in combination with cytotoxic therapies, where it is hoped that preclinical evidence of treatment synergy will translate into improved therapeutic efficacy. Results from these ongoing studies are keenly awaited.
authors.affiliation: Oxford Cancer Centre, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LE, UK. david.church@oncology.ox.ac.uk
authors.forename: David N
authors.initials: DN
authors.lastname: Church
authors.forename: Denis C
authors.initials: DC
authors.lastname: Talbot
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D002986:Clinical Trials as Topic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000077022:Survivin
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin