Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
Institute of Digestive Disease, State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China.
Int J Mol Sci. 2019 Nov 28;20(23):5999. doi: 10.3390/ijms20235999.
Colorectal cancer (CRC) is a kind of solid tumor and the third most common cancer type in the world. It is a heterogeneous disease characterized by genetic and epigenetic aberrations. The mutation is the key step driving the transition from adenoma to adenocarcinoma. The functional roles of mutation in tumor development have been comprehensively investigated. In CRC, mutation was associated with poor prognosis and chemoresistance. A gain of function (GOF) of p53 mutants promotes cell proliferation, migration and invasion through multiple mechanisms. Restoring wild type p53 function, depleting p53 mutants, or intervention by targeting the oncogenic downstreams provides potential therapeutic strategies. In this review, we comprehensively summarize the GOF of p53 mutants in CRC progression as well as in some other solid tumors, and discuss the current strategies targeting p53 mutants in malignancies.
结直肠癌（CRC）是一种实体瘤，是世界上第三常见的癌症类型。它是一种具有遗传和表观遗传异常特征的异质性疾病。 突变是驱动从腺瘤到腺癌转变的关键步骤。 突变在肿瘤发展中的功能作用已被全面研究。在 CRC 中， 突变与预后不良和化疗耐药有关。p53 突变体的功能获得（GOF）通过多种机制促进细胞增殖、迁移和侵袭。恢复野生型 p53 功能、耗尽 p53 突变体或通过靶向致癌下游进行干预提供了潜在的治疗策略。在这篇综述中，我们全面总结了 p53 突变体在 CRC 进展以及其他一些实体瘤中的功能获得作用，并讨论了针对恶性肿瘤中 p53 突变体的当前策略。
