Targeting p53 as a therapeutic strategy in sensitizing TRAIL-induced apoptosis in cancer cells.
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has been intensively studied as a cancer therapeutic agent due to its unique ability to induce apoptosis in malignant cells but not in normal cells. However, as more human cancer cells are reported to be resistant to TRAIL treatment, it is important to develop new therapeutic strategies to overcome this resistance. p53 is an important tumor suppressor that is widely involved in cellular responses to various stresses. In this mini-review, we aim to provide an overview of the intricate relationship between p53 and the TRAIL-mediated apoptosis pathway, and to summarize the current approaches of targeting p53 as a therapeutic strategy to sensitize TRAIL-induced apoptosis in human cancer cells. Although in some cases TRAIL kills cancer cells in a p53-independent manner, it is believed that in cancers with wild-type and functional p53, targeting p53 may be an important strategy for overcoming TRAIL-resistance in cancer therapy.
Department of Epidemiology and Public Health, Yong Loo Lin School of Medicine, National University of Singapore, 16 Medical Drive, Singapore, Republic of Singapore.
Jing
J
Zhao
Yixin
Y
Lu
Han-Ming
HM
Shen
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D004249:DNA Damage; D004260:DNA Repair; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D059808:Polyphenols / Q000494:pharmacology; D061988:Proteasome Inhibitors; D015398:Signal Transduction / Q000502:physiology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D014810:Vitamin E / Q000494:pharmacology
D000970:Antineoplastic Agents; D059808:Polyphenols; D061988:Proteasome Inhibitors; D053221:TNF-Related Apoptosis-Inducing Ligand; D016159:Tumor Suppressor Protein p53; D014810:Vitamin E