Targeting apoptosis in cancer chemotherapy.
Targeting apoptosis in cancer chemotherapy.
复制标题
DOI：
10.1517/14728222.6.1.73
复制
发表时间：
2002-02-01
影响因子：
5.8
通讯作者：
Makin, Guy
中科院分区：
文献类型：
--
作者：
Makin, Guy
癌症生物学的目的是更好地了解癌症的分子基础，期望这将导致治疗进展和改善患者的预后。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，并导致了对化疗方式的改变。现在越来越多的人认为，常规化疗药物的部分疗效是由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本理解的进步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，其中关于生与死的细胞决定可以被视为由Bcl-2家族的蛋白质成员制定的促凋亡信号和抗凋亡信号的平衡的结果，控制线粒体细胞色素c的释放。这一框架允许提供死亡信号和废除生存信号的重要性得到赞赏。一系列新的方法来诱导细胞凋亡下调生存信号。此外，许多替代策略，旨在针对特定的肿瘤细胞的分子异常作为诱导细胞凋亡的手段也正在调查中，其中几个进行了讨论。对细胞死亡机制的理解将对肿瘤学的实践和许多患者的前景产生深远的影响。
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.