Recent advances in targeting regulators of apoptosis in cancer cells for therapeutic gain.
Apoptosis is a fundamental cellular death process that is essential for normal tissue homeostasis, whose deregulation is associated with several human disease states, including cancer. Increased understanding of cancer biology has led to the hypothesis that although cancer cells are inherently resistant to the engagement of apoptosis due to the deregulation of molecular components of core apoptotic machinery or of survival signalling cascades, they are primed to die as a result of microenvironmental and oncogenic proapoptotic stress. Recently, deeper insight into the molecular regulation of apoptosis and, specifically, into its deregulation in cancer has led to the development of promising therapies to restore apoptosis and enable selective tumour cell kill. It is hoped that these mechanism-based therapies will exhibit less problematic toxicity profiles than those of conventional agents. Moreover, the development of tailored therapies directed at malignancies bearing specific alterations in apoptotic or survival signalling components may be used in combination approaches to overcome the resistance to other forms of treatment.
Taylor
Kathryn
K
Paterson Institute for Cancer Research, Clinical and Experimental Pharmacology Group, University of Manchester, Wilmslow Road, Withington, Manchester, M20 4BX, UK.
Micha
Dimitra
D
Ranson
Malcolm
M
Dive
Caroline
C
D000470:Alkaloids / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D053119:Benzophenanthridines / Q000494:pharmacology / Q000627:therapeutic use; D020169:Caspases / Q000378:metabolism; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use; D013873:Thionucleotides / Q000235:genetics / Q000378:metabolism; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics / Q000378:metabolism; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
D000470:Alkaloids; D000970:Antineoplastic Agents; D053119:Benzophenanthridines; D020169:Caspases; D016376:Oligonucleotides, Antisense; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; D013873:Thionucleotides; D051636:X-Linked Inhibitor of Apoptosis Protein; D051020:bcl-X Protein; C408162:oblimersen; C016299:chelerythrine