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IAP proteins as targets for drug development in oncology

Authors Dubrez L, Berthelet J, Glorian V

Received 27 April 2013

Accepted for publication 17 May 2013

Published 16 September 2013 Volume 2013:6 Pages 1285—1304


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Laurence Dubrez,1,2 Jean Berthelet,1,2 Valérie Glorian,1,2

1Institut National de la Santé et de la Recherche Médicale (Inserm), Dijon, France; 2Université de Bourgogne, Dijon, France

Abstract: The inhibitors of apoptosis (IAPs) constitute a family of proteins involved in the regulation of various cellular processes, including cell death, immune and inflammatory responses, cell proliferation, cell differentiation, and cell motility. There is accumulating evidence supporting IAP-targeting in tumors: IAPs regulate various cellular processes that contribute to tumor development, such as cell death, cell proliferation, and cell migration; their expression is increased in a number of human tumor samples, and IAP overexpression has been correlated with tumor growth, and poor prognosis or low response to treatment; and IAP expression can be rapidly induced in response to chemotherapy or radiotherapy because of the presence of an internal ribosome entry site (IRES)-dependent mechanism of translation initiation, which could contribute to resistance to antitumor therapy. The development of IAP antagonists is an important challenge and was subject to intense research over the past decade. Six molecules are currently in clinical trials. This review focuses on the role of IAPs in tumors and the development of IAP-targeting molecules for anticancer therapy.

Keywords: Smac mimetics, apoptosis, antitumor therapy

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