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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.

Original publication

DOI

10.1007/s11912-012-0215-2

Type

Journal article

Journal

Curr Oncol Rep

Publication Date

04/2012

Volume

14

Pages

120 - 128

Keywords

Antineoplastic Agents, Apoptosis, Cell Cycle, Clinical Trials as Topic, Humans, Inhibitor of Apoptosis Proteins, Neoplasms, Survivin