title: P53 mutations in colorectal cancer - molecular pathogenesis and pharmacological reactivation.
abstract: Colorectal cancer (CRC) is one of the most common malignancies with high prevalence and low 5-year survival. CRC is a heterogeneous disease with a complex, genetic and biochemical background. It is now generally accepted that a few important intracellular signaling pathways, including Wnt/β-catenin signaling, Ras signaling, and p53 signaling are frequently dysregulated in CRC. Patients with mutant p53 gene are often resistant to current therapies, conferring poor prognosis. Tumor suppressor p53 protein is a transcription factor inducing cell cycle arrest, senescence, and apoptosis under cellular stress. Emerging evidence from laboratories and clinical trials shows that some small molecule inhibitors exert anti-cancer effect via reactivation and restoration of p53 function. In this review, we summarize the p53 function and characterize its mutations in CRC. The involvement of p53 mutations in pathogenesis of CRC and their clinical impacts will be highlighted. Moreover, we also describe the current achievements of using p53 modulators to reactivate this pathway in CRC, which may have great potential as novel anti-cancer therapy.
authors.affiliation: Xiao-Lan Li, Jianbiao Zhou, Wee-Joo Chng, Cancer Science Institute of Singapore, National University of Singapore, 14 Medical Drive, Centre for Translational Medicine, Singapore 117599, Singapore.
authors.forename: Xiao-Lan
authors.initials: XL
authors.lastname: Li
authors.affiliation: Xiao-Lan Li, Jianbiao Zhou, Wee-Joo Chng, Cancer Science Institute of Singapore, National University of Singapore, 14 Medical Drive, Centre for Translational Medicine, Singapore 117599, Singapore.
authors.forename: Jianbiao
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Xiao-Lan Li, Jianbiao Zhou, Wee-Joo Chng, Cancer Science Institute of Singapore, National University of Singapore, 14 Medical Drive, Centre for Translational Medicine, Singapore 117599, Singapore.
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Chen
authors.affiliation: Xiao-Lan Li, Jianbiao Zhou, Wee-Joo Chng, Cancer Science Institute of Singapore, National University of Singapore, 14 Medical Drive, Centre for Translational Medicine, Singapore 117599, Singapore.
authors.forename: Wee-Joo
authors.initials: WJ
authors.lastname: Chng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D059447:Cell Cycle Checkpoints; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D010641:Phenotype; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Colorectal cancer; Gene therapy; PRIMA-1MET; Small molecule inhibitor; Tumor suppressor; p53