small molecule inhibitors of bcl-2 family proteins for pancreatic cancer therapybcl - 2家族蛋白的小分子抑制剂对胰腺癌的治疗.pdf

Cancers 2011, 3, 1527-1549; doi:10.3390/cancers3021527 OPEN ACCESS cancer ISSN 2072-6694 /journal/cancers Review Small Molecule Inhibitors of Bcl-2 Family Proteins for Pancreatic Cancer Therapy Ashiq Masood 1,†, Asfar S. Azmi 2,† and Ramzi M. Mohammad 1,3,* 1 Department of Internal Medicine/Pathology, Karmanos Cancer Institute, Wayne State University, 4100 John R, HWCRC 732, Detroit, MI 48201, USA; E-Mail: amasood@ 2 Department of Pathology, Karmanos Cancer Institute, Wayne State University, 4100 John R, HWCRC 732, Detroit MI 48201, USA; E-Mail: azmia@ 3 Department of Oncology, Karmanos Cancer Institute, 4100 John R, HWCRC 732, Detroit, MI 48201, USA † These authors contributed equally to this work. * Author to whom correspondence should be addressed; E-Mail: mohammar@; Tel.: +1-313-576-8329; Fax: +1-313-576-8389. Received: 18 February 2011; in revised form: 24 February 2011 / Accepted: 16 March 2011 / Published: 24 March 2011 Abstract: Pancreatic cancer (PC) has a complex etiology and displays a wide range of cellular escape pathways that allow it to resist different treatment modalities. Crucial signaling molecules that function downstream of the survival pathways, particularly at points where several of these pathways crosstalk, provide valuable targets for the development of novel anti-cancer drugs. Bcl-2 family member proteins are anti-apoptotic molecules that are known to be overexpressed in most cancers inclu