Apoptosis and cancer chemotherapy.
The explosion of interest in apoptosis amongst cancer biologists has been underpinned by the hope that a mechanistic understanding of cell death will inform our understanding of tumour drug resistance. A framework for drug-induced apoptosis can now be described in which a balance exists between intrinsic and extrinsic survival signals and drug-induced death signals. Pro- and anti-apoptotic signals impact upon pro-apoptotic members of the Bcl-2 family of proteins, which ultimately control the cellular fate. This framework suggests multiple points at which therapeutic interventions could be made to overcome drug resistance and, in addition, generates novel molecular targets for the induction of apoptosis in cancer cells.
Makin
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CRC Molecular and Cellular Pharmacology Group, School of Biological Sciences, G38 Stopford Building, Oxford Road, Manchester, UK M13 9PT. guy.makin@man.ac.uk
Dive
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D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002518:Ceramides / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*
D000970:Antineoplastic Agents; D002518:Ceramides; D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2; D018844:Cyclin-Dependent Kinases