APO2 ligand/tumor necrosis factor-related apoptosis-inducing ligand in prostate cancer therapy.
Prostate cancer is one of the most common cancers in men and is the second leading cause of cancer-related death in the USA. Many anti-tumor agents against prostate cancer cells have been developed, but their unacceptable systemic toxicity to normal tissues usually limits their use in the clinic. Apo2 ligand (Apo2L), also called Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), is one of several members of the TNF gene superfamily that induces apoptosis through engagement of death receptors. This protein has generated tremendous enthusiasm as a potential tumor-specific cancer therapeutic because, as a stable trimer, it selectively induces apoptosis in many transformed cells, but not in most normal cells. In this review we discuss its potential use in prostate cancer therapy, the mechanisms by which induces apoptosis or that underlie resistance to it, and strategies for sensitization to overcome them. Conventional chemotherapeutic and chemopreventive drugs, irradiation, and other therapeutic agents, such as histone deacetylase inhibitors or retinoids can sensitize Apo2L/TRAIL-resistant cells and tumors. Investigating the apoptotic effects of Apo2L/TRAIL, a unique tumor-specific cell death ligand, now in clinical trials, alone or in combination may not only help in understanding its antineoplastic role in prostate carcinoma but may also provide insights into basic mechanisms of apoptosis.
Bucur
Octavian
O
Department of Cancer Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Ray
Subrata
S
Bucur
Maria Cristina
MC
Almasan
Alexandru
A
D000728:Androgens / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D016923:Cell Death; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival; D002986:Clinical Trials as Topic; D004791:Enzyme Inhibitors / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012176:Retinoids / Q000737:chemistry; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000728:Androgens; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D008024:Ligands; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D012176:Retinoids; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D006655:Histone Deacetylases