PDF(Pubmed)
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.
METHODS: 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.
CONCLUSIONS: 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.
METHODS: 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.
CONCLUSIONS: 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.
摘要：
背景：胞内蛋白的酪氨酸磷酸化是一种翻译后修饰，在细胞事件期间的信号转导中起调节作用。由蛋白酪氨酸磷酸酶（PTP）引起的信号转导蛋白的去磷酸化作用是它们作为会聚节点介导信号通路之间的串扰的作用。在癌症的背景下，PTP介导的途径已被鉴定为使癌细胞能够减轻由临床治疗引起的应激的信号传导中心。这是通过促进生长刺激信号通路的组成型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，当与PTP抑制剂联合使用时，抗癌药物将释放其最大的治疗效力。逆转导致癌症治疗期间临床失败的耐药性。
方法：这篇综述旨在阐述支持PTP介导的通路参与靶向治疗和免疫检查点治疗抗性发展的最新见解。
结论：这篇综述提出了在抗癌联合治疗中抑制PTP的概念，作为临床上实现长期肿瘤消退的潜在策略。目前正在进行临床试验，以评估联合治疗在晚期肿瘤中的安全性和有效性。
方法：这篇综述旨在阐述支持PTP介导的通路参与靶向治疗和免疫检查点治疗抗性发展的最新见解。
结论：这篇综述提出了在抗癌联合治疗中抑制PTP的概念，作为临床上实现长期肿瘤消退的潜在策略。目前正在进行临床试验，以评估联合治疗在晚期肿瘤中的安全性和有效性。
