Apoptosis and cancer: strategies for integrating programmed cell death.
Virtually all human cells are endowed with the capacity to commit suicide using an evolutionarily conserved mechanism that involves activation of caspase-family cell death proteases. Caspase activation culminates in a cell death process known as "apoptosis." The activation of these intracellular proteases is carefully controlled through a delicate balance of anti- and pro-death proteins, serving to precisely regulate cell life span. Defects in the natural death pathway promote tumorigenesis by prolonging cell life span and hence cell accumulation. Low-grade B-cell malignancies, particularly follicular lymphoma and chronic lymphocytic leukemia (CLL) represent quintessential examples of human neoplasms characterized primarily by a problem with cell death rather than cell cycle. Because the cell suicide pathway is also required for tumor eradication by the immune system, anticancer drugs, and irradiation, cancer-associated defects in the cellular apoptosis machinery also play an important role in treatment failures. Monoclonal antibody-based therapies may provide opportunities to either bypass defects in apoptosis pathways or to activate latent apoptotic programs in cancer cells, particularly in lymphoid malignancies where tissue-specific antigens can be exploited for cell-selective activation of apoptosis. Recent knowledge about apoptosis pathways is reviewed, and some examples of opportunities for therapeutic intervention are discussed.
Reed
C J
CJ
The Burnham Institute, La Jolla, CA 92037, USA.
D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D016393:Lymphoma, B-Cell / Q000473:pathology*; D008928:Mitochondria / Q000502:physiology; D009369:Neoplasms / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology
D019253:Proto-Oncogene Proteins c-bcl-2; D018124:Receptors, Tumor Necrosis Factor; D020169:Caspases