Department of Surgery, University of California Medical Center, Sacramento, California 95817, USA.
J Surg Res. 2010 Dec;164(2):301-8. doi: 10.1016/j.jss.2009.07.011. Epub 2009 Aug 7.
Apoptosis has long been recognized as a critical mechanism of programmed cell death that is preserved among all eukaryotes and is involved in a variety of disease processes. Malignant transformation of cells is associated with a constellation of pro-survival mutations rendering them resistant to apoptosis. Traditional cancer therapy evokes cell death by inducing apoptosis; however, the apoptotic resistance inherent in cancer cells has been a significant barrier to effective chemotherapy. More recently, other mechanisms of cell death have emerged as potential novel mechanisms for cancer therapies to induce cell death, either in addition to, or instead of, apoptosis-induced cytotoxic treatment. Autophagy is a process that occurs in all cells, but is induced in many types of cancer. Autophagy functions as both a cell survival and a cell death mechanism depending on the context and the stimuli, which are likely exploitable for cancer therapy. Anoikis is also a physiologic process in normal cells used to maintain homeostasis, in which cell death is induced in response to loss of extracellular membrane (ECM) attachment. Cancer cells are notoriously resistant to anoikis, enabling metastasis and new tumor growth beyond their original environment. Interestingly, autophagy may actually by a major contributor to anoikis resistance in cancer. As these two processes are elucidated in more detail, there is great potential for novel targets that affect cancer cell death, in addition to the current cytotoxic agents.
细胞凋亡一直被认为是一种重要的程序性细胞死亡机制，存在于所有真核生物中，并参与多种疾病过程。细胞的恶性转化与一系列促进生存的突变有关，使它们对细胞凋亡产生抗性。传统的癌症治疗通过诱导细胞凋亡来引发细胞死亡；然而，癌细胞固有的凋亡抵抗已成为有效化疗的一个重大障碍。最近，其他细胞死亡机制已成为癌症治疗的潜在新机制，以诱导细胞死亡，无论是作为凋亡诱导细胞毒性治疗的补充，还是替代。自噬是一种发生在所有细胞中的过程，但在许多类型的癌症中被诱导。自噬既是一种细胞生存机制，也是一种细胞死亡机制，这取决于具体情况和刺激因素，这些因素可能可用于癌症治疗。失巢凋亡也是正常细胞中用于维持体内平衡的一种生理过程，其中细胞死亡是对外界细胞膜 (ECM) 附着丧失的反应。癌细胞对失巢凋亡具有明显的抗性，使其能够转移并在其原始环境之外生长新的肿瘤。有趣的是，自噬实际上可能是癌细胞失巢凋亡抗性的主要原因。随着这两个过程被更详细地阐明，除了目前的细胞毒性药物外，还有很大的潜力针对影响癌细胞死亡的新靶点。
