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Open Access Highly Accessed Review

Targeting p53 by small molecules in hematological malignancies

Manujendra N Saha12, Lugui Qiu3 and Hong Chang124*

Author Affiliations

1 Division of Molecular and Cellular Biology, Toronto General Research Institute, Toronto, Canada

2 Dept. of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Canada

3 Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China

4 Dept. of Laboratory Hematology and Medical Oncology, University Health Network, Toronto, Ontario, Canada

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Journal of Hematology & Oncology 2013, 6:23  doi:10.1186/1756-8722-6-23

Published: 27 March 2013

Abstract

p53 is a powerful tumor suppressor and is an attractive cancer therapeutic target. A breakthrough in cancer research came from the discovery of the drugs which are capable of reactivating p53 function. Most anti-cancer agents, from traditional chemo- and radiation therapies to more recently developed non-peptide small molecules exert their effects by enhancing the anti-proliferative activities of p53. Small molecules such as nutlin, RITA, and PRIMA-1 that can activate p53 have shown their anti-tumor effects in different types of hematological malignancies. Importantly, nutlin and PRIMA-1 have successfully reached the stage of phase I/II clinical trials in at least one type of hematological cancer. Thus, the pharmacological activation of p53 by these small molecules has a major clinical impact on prognostic use and targeted drug design. In the current review, we present the recent achievements in p53 research using small molecules in hematological malignancies. Anticancer activity of different classes of compounds targeting the p53 signaling pathway and their mechanism of action are discussed. In addition, we discuss how p53 tumor suppressor protein holds promise as a drug target for recent and future novel therapies in these diseases.

Keywords:
Hematological malignancies; Leukemia; Lymphoma; Myeloma; p53; Nutlin; RITA; PRIMA-1; MIRA-1; Apoptosis