Apoptosis-based therapies for hematologic malignancies.
Apoptosis is an intrinsic cell death program that plays critical roles in tissue homeostasis, especially in organs where high rates of daily cell production are offset by rapid cell turnover. The hematopoietic system provides numerous examples attesting to the importance of cell death mechanisms for achieving homeostatic control. Much has been learned about the mechanisms of apoptosis of lymphoid and hematopoietic cells since the seminal observation in 1980 that glucocorticoids induce DNA fragmentation and apoptosis of thymocytes and the demonstration in 1990 that depriving colony-stimulating factors from factor-dependent hematopoietic cells causes programmed cell death. From an understanding of the core components of the apoptosis machinery at the molecular and structural levels, many potential new therapies for leukemia and lymphoma are emerging. In this review, we introduce some of the drug discovery targets thus far identified within the core apoptotic machinery and describe some of the progress to date toward translating our growing knowledge about these targets into new therapies for cancer and leukemia.
Reed
John C
JC
Burnham Institute, 10901 N Torrey Pines Rd, La Jolla, CA 92037, USA. reedoffice@burnham.org
Pellecchia
Maurizio
M
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015195:Drug Design; D015870:Gene Expression / Q000187:drug effects; D019254:Genes, bcl-2 / Q000187:drug effects; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008954:Models, Biological; D015394:Molecular Structure; D011506:Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D000970:Antineoplastic Agents; D051034:Inhibitor of Apoptosis Proteins; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha