Recent advances in understanding apoptosis: new therapeutic opportunities in cancer chemotherapy.
Major advances have been made in our understanding of the regulation of the molecular machinery of apoptosis in vitro. Molecules linking proliferation and apoptosis in healthy cells are being identified and here apoptotic cell death provides the 'fail-safe' mechanism to counteract excess proliferation. More recently, pioneering work on the regulation of apoptosis, in animal models of tumour development, has shown that suppression of apoptosis in the presence of a proliferative stimulus is sufficient for tumour development. Progress has also been made towards clarifying the contribution of drug-induced apoptosis to tumour response. With increasing evidence that failure to engage apoptosis after drug treatment contributes to drug resistance in vivo comes renewed confidence that new therapeutic approaches based on drug targets in apoptotic pathways will improve the treatment of cancer patients. As ever, tumour specificity is the major issue to be resolved.
Makin
Guy
G
Cancer Research UK, Molecular and Cellular Pharmacology Group, School of Biological Sciences, University of Manchester, Manchester, UK M13 9PT.
Dive
Caroline
C
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins; D019008:Drug Resistance, Neoplasm; D019254:Genes, bcl-2; D016259:Genes, myc / Q000502:physiology; D006023:Glycoproteins / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D051379:Mice; D015513:Oncogene Proteins / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000494:pharmacology; D025521:Tumor Suppressor Proteins / Q000378:metabolism / Q000494:pharmacology
D000970:Antineoplastic Agents; D015938:Complement Membrane Attack Complex; D006023:Glycoproteins; D015513:Oncogene Proteins; C047610:SC5b-9 protein complex; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D003165:Complement System Proteins; D020169:Caspases