Makin Guy
CRC Molecular and Cellular Pharmacology Group, School of Biological Sciences, and Medical School, University of Manchester, Manchester, UK.
Expert Opin Ther Targets. 2002 Feb;6(1):73-84. doi: 10.1517/14728222.6.1.73.
The aim of cancer biology is for a better understanding of the molecular basis of cancer, with the expectation that this will result in therapeutic advances and improved outcomes for patients. The discovery of apoptosis has contributed much to our understanding of the mechanisms of cell death, in both normal and neoplastic cells, and it has led to changes in the way that chemotherapy has been viewed. It is now increasingly accepted that part of the efficacy of conventional chemotherapeutic drugs is due to their ability to induce apoptosis, although this area is not without controversy. This has allowed advances in the fundamental understanding of apoptosis to have similar impacts upon cancer biology. It is now possible to construct a framework where cellular decisions about life and death can be seen as the result of a balance of pro- and anti-apoptotic signals, enacted by protein members of the Bcl-2 family, controlling mitochondrial cytochrome c release. This framework has allowed the importance of providing death signals and abrogating survival signals to both be appreciated. A range of novel approaches to the induction of apoptosis by downregulating survival signalling are described. In addition, many alternative strategies aimed at targeting particular molecular abnormalities of neoplastic cells as a means of inducing apoptosis are also under investigation and several of these are discussed. The mechanistic understanding of cell death will have profound impacts upon the practice of oncology and outlook for many patients.
癌症生物学的目标是更好地理解癌症的分子基础，期望这将带来治疗进展并改善患者的预后。细胞凋亡的发现极大地促进了我们对正常细胞和肿瘤细胞中细胞死亡机制的理解，并且它导致了人们对化疗看法的改变。现在越来越多人认为，传统化疗药物的部分疗效归因于它们诱导细胞凋亡的能力，尽管这一领域并非没有争议。这使得对细胞凋亡的基础理解取得的进展对癌症生物学产生了类似的影响。现在有可能构建一个框架，在这个框架中，细胞关于生死的决定可以被视为由Bcl-2家族蛋白成员调控线粒体细胞色素c释放所产生的促凋亡信号和抗凋亡信号平衡的结果。这个框架使人们认识到提供死亡信号和消除生存信号的重要性。本文描述了一系列通过下调生存信号来诱导细胞凋亡的新方法。此外，许多旨在针对肿瘤细胞特定分子异常以诱导细胞凋亡的替代策略也在研究中，本文将讨论其中的几种。对细胞死亡的机制性理解将对肿瘤学实践和许多患者的前景产生深远影响。
