Meng Xuan, Franklin Derek A, Dong Jiahong, Zhang Yanping
Department of Radiation Oncology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Hospital and Institute of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing, China. Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, China.
Department of Radiation Oncology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Cancer Res. 2014 Dec 15;74(24):7161-7. doi: 10.1158/0008-5472.CAN-14-1446. Epub 2014 Dec 4.
Abnormalities in the TP53 gene and overexpression of MDM2, a transcriptional target and negative regulator of p53, are commonly observed in cancers. The MDM2-p53 feedback loop plays an important role in tumor progression and thus, increased understanding of the pathway has the potential to improve clinical outcomes for cancer patients. Hepatocellular carcinoma (HCC) has emerged as one of the most commonly diagnosed forms of human cancer; yet, the current treatment for HCC is less effective than those used against other cancers. We review the current studies of the MDM2-p53 pathway in cancer with a focus on HCC and specifically discuss the impact of p53 mutations along with other alterations of the MDM2-p53 feedback loop in HCC. We also discuss the potential diagnostic and prognostic applications of p53 and MDM2 in malignant tumors as well as therapeutic avenues that are being developed to target the MDM2-p53 pathway.
TP53基因异常以及MDM2（p53的转录靶点和负调节因子）的过表达在癌症中普遍存在。MDM2-p53反馈环在肿瘤进展中起重要作用，因此，对该通路的深入了解有可能改善癌症患者的临床结局。肝细胞癌（HCC）已成为人类癌症中最常见的诊断形式之一；然而，目前针对HCC的治疗效果不如针对其他癌症的治疗效果。我们回顾了目前关于癌症中MDM2-p53通路的研究，重点是HCC，并特别讨论了p53突变以及HCC中MDM2-p53反馈环的其他改变的影响。我们还讨论了p53和MDM2在恶性肿瘤中的潜在诊断和预后应用，以及正在开发的针对MDM2-p53通路的治疗途径。
