Apoptosis and non-apoptotic deaths in cancer development and treatment response.
Resistance to apoptosis is closely linked to tumorigenesis, as it enables malignant cells to expand even in a stressful environment. Cells resistant to apoptosis are also assumed to be resistant to anti-cancer therapies. Apoptosis has therefore taken a central position in cell death research. However, its contribution to treatment success is highly debated for solid tumors. It becomes more and more clear that cells can also die by non-apoptotic mechanisms, such as autophagy, mitotic catastrophe and necrosis. In this review, we summarize the current knowledge regarding the molecular pathways that underlie these apoptotic and non-apoptotic death pathways, and discuss the clinical data that have now accumulated to evaluate their roles in tumor development and cancer treatment.
de Bruin
Elza C
EC
Laboratory for Experimental Oncology and Radiobiology, Center for Experimental Molecular Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. E.C.deBruin@amc.uva.nl
Medema
Jan Paul
JP
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D051033:Apoptosis Inducing Factor / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000235:genetics; D016923:Cell Death / Q000187:drug effects* / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D016503:Drug Delivery Systems; D006801:Humans; D009336:Necrosis / Q000235:genetics / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality*; D010597:Pharmacogenetics; D012680:Sensitivity and Specificity; D015398:Signal Transduction; D016019:Survival Analysis
D000970:Antineoplastic Agents; D051033:Apoptosis Inducing Factor