Induction of apoptosis in cancer: new therapeutic opportunities.
Autonomous cell proliferation is one of the hallmarks of cancer cells, driven by activated growth-promoting oncogenes. However, deregulated activation of these oncogenes also triggers apoptosis via multiple pathways. Among them, the ARF-p53 pathway appears to play a major role in mediating oncogene-induced apoptosis. Consequently, suppression of apoptosis by inactivation of p53 and other tumor suppressors is central to tumor development. These findings have broad implications in understanding cancer genetics and therapy. They help define the roles for oncogenes and tumor suppressor genes in tumorigenesis. Furthermore, the notion that cancer cells often carry specific defects in apoptotic pathways but are inherently sensitive to apoptosis as a result of deregulated proliferation, offers numerous opportunities for manipulating apoptosis in directions of clinical application.
Ding
Han-Fei
HF
Department of Biochemistry and Molecular Biology, Medical College of Ohio, Toledo, OH, USA.
Fisher
David E
DE
D017209:Apoptosis / Q000502:physiology*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins / Q000502:physiology; D061945:Caspase Inhibitors; D020169:Caspases / Q000502:physiology; D018797:Cell Cycle Proteins; D004249:DNA Damage / Q000502:physiology; D004268:DNA-Binding Proteins; D015536:Down-Regulation / Q000502:physiology; D050684:E2F Transcription Factors; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D008928:Mitochondria / Q000502:physiology; D009369:Neoplasms / Q000503:physiopathology*; D015689:Oncogene Protein p21(ras) / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; D061945:Caspase Inhibitors; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D019869:Phosphatidylinositol 3-Kinases; D020169:Caspases; D015689:Oncogene Protein p21(ras)