Protein tyrosine phosphatases: emerging role in cancer therapy resistance.

Abstract

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. 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. 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.