Tan Ting-Ting, White Eileen
Center for Advanced Biotechnology and Medicine and Rutgers University, Piscataway, NJ 08854, USA.
Adv Exp Med Biol. 2008;615:81-104. doi: 10.1007/978-1-4020-6554-5_5.
Defects in apoptosis that evolve during the course of cancer progression not only provide cancer cells with intrinsic survival advantage, but also provide inherent resistance to chemotherapeutic agents. Thus, modulation of apoptosis by targeting components of the apoptotic machinery and its regulators to restore apoptotic function is a rational approach for treating cancer. With our increasing knowledge of the mechanisms of apoptosis regulation and of how apoptosis is disabled in cancer cells, numerous novel approaches targeting apoptotic pathways can now be exploited for cancer therapy. While most of these therapies are still in preclinical development, some have shown considerable promise and progressed into the clinic. This chapter summarizes the current knowledge of the apoptotic pathways and provides a selective review on the development of drugs that target the apoptotic machinery.
在癌症进展过程中发生的细胞凋亡缺陷不仅赋予癌细胞内在的生存优势,还使其对化疗药物具有固有抗性。因此,通过靶向凋亡机制及其调节因子的成分来调节细胞凋亡以恢复凋亡功能是一种合理的癌症治疗方法。随着我们对细胞凋亡调节机制以及癌细胞中细胞凋亡如何被抑制的认识不断增加,现在有许多针对凋亡途径的新方法可用于癌症治疗。虽然这些疗法大多仍处于临床前开发阶段,但有些已显示出相当大的前景并进入了临床阶段。本章总结了目前对凋亡途径的认识,并对靶向凋亡机制的药物开发进行了选择性综述。