Ciccarese Chiara, Massari Francesco, Blanca Ana, Tortora Giampaolo, Montironi Rodolfo, Cheng Liang, Scarpelli Marina, Raspollini Maria R, Vau Nuno, Fonseca Jorge, Lopez-Beltran Antonio
a Medical Oncology, Azienda Ospedaliera Universitaria Integrata , University of Verona , Verona , Italy.
b Medical Oncology , Azienda Ospedaliera Universitaria Integrata (A.O.U.I.) , Verona , Italy.
Expert Opin Ther Targets. 2017 Apr;21(4):401-414. doi: 10.1080/14728222.2017.1297798. Epub 2017 Mar 1.
Despite more than 30 years of research on p53 resulting in >50,000 publications, we are now beginning to figure out the complexity of the p53 pathway, gene ontology and conformational structure of the molecule. Recent years brought great advances in p53 related drugs and the potencial ways in which p53 is inactivated in cancer. Areas covered: We searched for related publications on Pubmed and ClinicalTrial.gov using the following keywords 'p53, Tp53, p53 and bladder cancer, p53 and therapeutic target'. Relevant articles improved the understanding on p53 pathways and their potential as candidate to targeted therapy in bladder cancer. Expert opinion: Novel strategies developed to restore the function of mutants with chemical chaperones or by using compounds to improved pharmacokinetic properties are in development with potential to be applied in the oncology clinic. Other strategies targeting aberrantly overexpressed p53 regulators with wild-type p53 are also an active area of research. In particular, studies inhibiting the interaction of p53 with its negative regulators MDMX and MDM2 are an important field in drug discovery. Small molecules for inhibition of MDM2 are now in clinical trials process. However, personalized anticancer therapy might eventually advance through analyses of p53 status in cancer patients.
尽管对p53进行了30多年的研究,相关出版物超过5万篇,但我们现在才开始弄清楚p53信号通路的复杂性、该分子的基因本体论和构象结构。近年来,p53相关药物以及p53在癌症中失活的潜在方式取得了巨大进展。涵盖领域:我们在PubMed和ClinicalTrial.gov上使用以下关键词“p53、Tp53、p53与膀胱癌、p53与治疗靶点”搜索了相关出版物。相关文章增进了我们对p53信号通路及其作为膀胱癌靶向治疗候选靶点潜力的理解。专家观点:利用化学伴侣恢复突变体功能或使用化合物改善药代动力学性质的新策略正在研发中,有望应用于肿瘤临床。其他针对野生型p53异常过表达的p53调节因子的策略也是一个活跃的研究领域。特别是,抑制p53与其负调节因子MDMX和MDM2相互作用的研究是药物发现的一个重要领域。抑制MDM2的小分子目前正处于临床试验阶段。然而,个性化抗癌治疗最终可能通过分析癌症患者的p53状态取得进展。