Relation of apoptosis to cancer therapy.
Apoptosis, or programmed cell death, is a mode of cell death characterized by distinctive biochemical and morphological features that include endonuclease activation, chromatin condensation and margination, and cellular shrinkage and fragmentation. Its role is homeostatic regulation essential in the maintenance of renewable tissues; the process is controlled by the interaction of genes and tissue-specific hormones or growth factors. A number of apoptosis-regulating genes have recently been discovered including bc1-2, c-myc, and p53. Recent experimental evidence suggests that apoptosis plays an important role in regulation of tumor growth and tumor response to various forms of cancer therapy, including radiotherapy and chemotherapy. Apoptosis develops rapidly, within hours, after cytotoxic treatments and is dose dependent. The apoptotic response correlates well with the antitumor efficacy of radiation and chemotherapy, which makes it a candidate predictor of tumor treatment response. Tumors vary in their apoptotic response to cytotoxic agents, with carcinomas being more responsive than sarcomas. In addition to this intertumor heterogeneity, there is also significant intratumor heterogeneity in apoptosis induction, consistent with the idea that the propensity for apoptosis is genetically regulated. Regulating apoptosis might be an effective way to improve tumor therapy; therapeutic gain would be achieved by increasing apoptotic response of tumors or by inhibiting apoptotic response of normal tissues.
Milas
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Department of Experimental Radiotherapy, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Stephens
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LC
Meyn
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D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D016158:Genes, p53; D006801:Humans; D009369:Neoplasms / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*
D000970:Antineoplastic Agents