Department of Internal Medicine/Pathology, Karmanos Cancer Institute, Wayne State University, 4100 John R, HWCRC 732, Detroit, MI 48201, USA.
Cancers (Basel). 2011 Jun 1;3(2):1527-49. doi: 10.3390/cancers3021527.
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 including PC. The anti-apoptotic machinery has been linked to the observed resistance developed to chemotherapy and radiation and therefore is important from the targeted drug development point of view. Over the past ten years, our group has extensively studied a series of small molecule inhibitors of Bcl-2 against PC and provide solid preclinical platform for testing such novel drugs in the clinic. This review examines the efficacy, potency, and function of several small molecule inhibitor drugs targeted to the Bcl-2 family of proteins and their preclinical progress against PC. This article further focuses on compounds that have been studied the most and also discusses the anti-cancer potential of newer class of Bcl-2 drugs.
胰腺癌（PC）的病因复杂，表现出多种细胞逃逸途径，使其能够抵抗不同的治疗方式。在生存途径下游起作用的关键信号分子，特别是在这些途径相互作用的几个点上，为开发新型抗癌药物提供了有价值的靶点。Bcl-2 家族成员蛋白是抗凋亡分子，已知在包括 PC 在内的大多数癌症中过度表达。抗凋亡机制与观察到的对化疗和放疗的耐药性有关，因此从靶向药物开发的角度来看非常重要。在过去的十年中，我们的研究小组广泛研究了一系列针对 Bcl-2 的小分子抑制剂来治疗 PC，并为在临床上测试这些新型药物提供了坚实的临床前平台。这篇综述考察了几种针对 Bcl-2 家族蛋白的小分子抑制剂药物的疗效、效力和功能，以及它们在 PC 方面的临床前进展。本文还进一步关注了研究最多的化合物，并讨论了新型 Bcl-2 药物的抗癌潜力。
