Protein tyrosine phosphatases: emerging role in cancer therapy resistance

IF 20.1 1区 医学 Q1 ONCOLOGY Cancer Communications Pub Date : 2024-05-13 DOI:10.1002/cac2.12548
Min Zhao, Wen Shuai, Zehao Su, Ping Xu, Aoxue Wang, Qiu Sun, Guan Wang
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Abstract

Background

Tyrosine phosphorylation of intracellular proteins is a post-translational modification that plays a regulatory role in signal transduction during cellular events. Dephosphorylation of signal transduction proteins caused by protein tyrosine phosphatases (PTPs) contributed their role as a convergent node to mediate cross-talk between signaling pathways. In the context of cancer, PTP-mediated pathways have been identified as signaling hubs that enabled cancer cells to mitigate stress induced by clinical therapy. This is achieved by the promotion of constitutive activation of growth-stimulatory signaling pathways or modulation of the immune-suppressive tumor microenvironment. Preclinical evidences suggested that anticancer drugs will release their greatest therapeutic potency when combined with PTP inhibitors, reversing drug resistance that was responsible for clinical failures during cancer therapy.

Areas covered

This review aimed to elaborate recent insights that supported the involvement of PTP-mediated pathways in the development of resistance to targeted therapy and immune-checkpoint therapy.

Expert opinion

This review proposed the notion of PTP inhibition in anticancer combination therapy as a potential strategy in clinic to achieve long-term tumor regression. Ongoing clinical trials are currently underway to assess the safety and efficacy of combination therapy in advanced-stage tumors.

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蛋白酪氨酸磷酸酶:在抗癌治疗中的新角色。
背景:细胞内蛋白质的酪氨酸磷酸化是一种翻译后修饰,在细胞事件的信号转导过程中发挥着调节作用。蛋白酪氨酸磷酸酶(PTPs)引起的信号转导蛋白的去磷酸化有助于它们发挥聚合节点的作用,介导信号通路之间的交叉对话。在癌症方面,PTP 介导的通路已被确定为信号枢纽,可使癌细胞减轻临床治疗引起的压力。这是通过促进生长刺激信号通路的组成性激活或调节免疫抑制性肿瘤微环境来实现的。临床前证据表明,抗癌药物与 PTP 抑制剂联合使用时将释放出最大的治疗效力,从而逆转导致癌症治疗临床失败的耐药性:本综述旨在阐述支持 PTP 介导的通路参与靶向疗法和免疫检查点疗法耐药性产生的最新观点:这篇综述提出了在抗癌联合疗法中抑制PTP的概念,将其作为实现长期肿瘤消退的潜在临床策略。目前正在进行临床试验,以评估联合疗法在晚期肿瘤中的安全性和有效性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cancer Communications
Cancer Communications Biochemistry, Genetics and Molecular Biology-Cancer Research
CiteScore
25.50
自引率
4.30%
发文量
153
审稿时长
4 weeks
期刊介绍: Cancer Communications is an open access, peer-reviewed online journal that encompasses basic, clinical, and translational cancer research. The journal welcomes submissions concerning clinical trials, epidemiology, molecular and cellular biology, and genetics.
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