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Current Oncology Reports

, Volume 14, Issue 2, pp 120–128 | Cite as

Survivin in Solid Tumors: Rationale for Development of Inhibitors

  • David N. Church
  • Denis C. TalbotEmail author
Evolving Therapies (RM Bukowski, Section Editor)

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.

Keywords

Survivin BIRC5 Apoptosis Cell cycle Cancer Solid tumours Antisense oligonucleotide 

Notes

Acknowledgment

Dr. Church and Dr. Talbot acknowledge financial support from Cancer Research UK.

Disclosure

D. N. Church: none; D. C. Talbot: advisory board member for Lilly UK, and honoraria and an unrestricted research grant from Lilly UK.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Oxford Cancer CentreChurchill HospitalOxfordUK

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