Wenge Wang1, Wafik S El-Deiry. 1. Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Abstract
PURPOSE OF REVIEW: p53 mutation occurs in over half of all human tumors. Among the remaining tumors, although they may process a wild-type p53, the pathways of p53-induced cell-cycle arrest and apoptosis are deficient. Therefore, p53 serves as a unique molecular target for cancer therapy. This review focuses on the current progress regarding restoration of p53 function in human tumors for molecularly targeted therapy. RECENT FINDINGS: Targeting p53 for cancer therapy has been intensively pursued. CP-31398 was the first small molecule identified with the ability to restore the wild-type conformation to mutant p53. Subsequently, PRIMA-1 and ellipticine were found to be able to induce mutant p53-dependent cell death. Nutlin was developed to rescue wild-type p53 from degradation mediated by MDM2. More recently, p53 family members can be activated and therefore serve as substitutes of p53 in tumor cells and induce cell death. SUMMARY: Loss of p53 function is a characteristic of almost all human tumors. Recent advances demonstrate that reconstitution of p53 function is possible and practical as a promising antitumor strategy.
PURPOSE OF REVIEW: p53 mutation occurs in over half of all humantumors. Among the remaining tumors, although they may process a wild-type p53, the pathways of p53-induced cell-cycle arrest and apoptosis are deficient. Therefore, p53 serves as a unique molecular target for cancer therapy. This review focuses on the current progress regarding restoration of p53 function in humantumors for molecularly targeted therapy. RECENT FINDINGS: Targeting p53 for cancer therapy has been intensively pursued. CP-31398 was the first small molecule identified with the ability to restore the wild-type conformation to mutant p53. Subsequently, PRIMA-1 and ellipticine were found to be able to induce mutant p53-dependent cell death. Nutlin was developed to rescue wild-type p53 from degradation mediated by MDM2. More recently, p53 family members can be activated and therefore serve as substitutes of p53 in tumor cells and induce cell death. SUMMARY: Loss of p53 function is a characteristic of almost all humantumors. Recent advances demonstrate that reconstitution of p53 function is possible and practical as a promising antitumor strategy.
Authors: Drew D Dudgeon; Sunita N Shinde; Tong Ying Shun; John S Lazo; Christopher J Strock; Kenneth A Giuliano; D Lansing Taylor; Patricia A Johnston; Paul A Johnston Journal: Assay Drug Dev Technol Date: 2010-08 Impact factor: 1.738
Authors: Jinfeng Shen; Ellen H van den Bogaard; Evelyn N Kouwenhoven; Vladimir J N Bykov; Tuula Rinne; Qiang Zhang; Geuranne S Tjabringa; Christian Gilissen; Simon J van Heeringen; Joost Schalkwijk; Hans van Bokhoven; Klas G Wiman; Huiqing Zhou Journal: Proc Natl Acad Sci U S A Date: 2013-01-25 Impact factor: 11.205