Melet Armelle, Song Keli, Bucur Octavian, Jagani Zainab, Grassian Alexandra R, Khosravi-Far Roya
Department of Pathology, Harvard Medical School, Beth Israel Deaconess Medical Center, 99 Brookline Avenue, Boston, MA 02215, USA.
Adv Exp Med Biol. 2008;615:47-79. doi: 10.1007/978-1-4020-6554-5_4.
Apoptosis is a cell suicide program that plays a critical role in development and tissue homeostasis. The ability of cancer cells to evade this programmed cell death (PCD) is a major characteristic that enables their uncontrolled growth. The efficiency of chemotherapy in killing such cells depends on the successful induction of apoptosis, since defects in apoptosis signaling are a major cause of drug resistance. Over the past decades, much progress has been made in our understanding of apoptotic signaling pathways and their dysregulation in cancer progression and therapy. These advances have provided new molecular targets for proapoptotic cancer therapies that have recently been used in drug development. While most of those therapies are still at the preclinical stage, some of them have shown much promise in the clinic. Here, we review our current knowledge of apoptosis regulation in cancer progression and therapy, as well as the new molecular targeted molecules that are being developed to reinstate cancer cell death.
细胞凋亡是一种细胞自杀程序,在发育和组织稳态中发挥关键作用。癌细胞逃避这种程序性细胞死亡(PCD)的能力是使其不受控制生长的主要特征。化疗杀死此类细胞的效率取决于能否成功诱导细胞凋亡,因为凋亡信号传导缺陷是耐药性的主要原因。在过去几十年里,我们对凋亡信号通路及其在癌症进展和治疗中的失调的理解取得了很大进展。这些进展为促凋亡癌症治疗提供了新的分子靶点,这些靶点最近已用于药物开发。虽然大多数此类疗法仍处于临床前阶段,但其中一些在临床上已显示出很大前景。在此,我们综述了目前关于癌症进展和治疗中细胞凋亡调控的知识,以及正在开发的用于恢复癌细胞死亡的新分子靶向分子。