Targeting apoptosis in cancer chemotherapy.
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.
Makin
Guy
G
CRC Molecular and Cellular Pharmacology Group, School of Biological Sciences, and Medical School, University of Manchester, Manchester, UK. guy.makin@man.ac.uk
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D016372:RNA, Antisense / Q000627:therapeutic use
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D016372:RNA, Antisense