Department of Pharmacology, Aarhus University, Denmark.
Curr Pharm Des. 2011;17(3):272-83. doi: 10.2174/138161211795049723.
Apoptosis plays an important role in development, growth, differentiation, altered gravity conditions, tissue homeostasis, immune defense, and cancer. It can be initiated by external signals via death receptors, but may also emerge from mitochondria. Today most of the key players in cellular apoptosis regulation are identified and can be targeted by therapeutic strategies. In this review we focus on recent development of drugs, which interfere with apoptosis and are currently used or tested for treatment of breast cancer. These novel agents include those targeting the extrinsic pathway such as Fas, tumor necrosis factor-alpha and tumor necrosis factor related apoptosis-inducing ligand, as well as drugs targeting the intrinsic Bcl-2 family pathway, or drugs inhibiting repair enzymes such as Poly (ADP-ribose) polymerase (PARP) inhibitors. Their function will be explained, their role in tumor biology and actual clinical studies will be discussed.
细胞凋亡在发育、生长、分化、改变重力条件、组织平衡、免疫防御和癌症中发挥着重要作用。它可以通过死亡受体被外部信号引发，也可能源自线粒体。如今，细胞凋亡调控的大多数关键因子已经被识别，并可以作为治疗策略的靶点。在这篇综述中，我们重点介绍了目前用于或正在临床试验中治疗乳腺癌的、干扰细胞凋亡的药物的最新进展。这些新型药物包括靶向外在途径的药物，如 Fas、肿瘤坏死因子-α和肿瘤坏死因子相关凋亡诱导配体，以及靶向内在 Bcl-2 家族途径的药物，或抑制修复酶的药物，如多聚（ADP-核糖）聚合酶（PARP）抑制剂。我们将解释它们的功能，讨论它们在肿瘤生物学中的作用和实际的临床研究。
