Checks and balances: Interplay of RTKs and PTPs in cancer progression

In recent years, targeted therapies for receptor tyrosine kinases (RTKs) have shown initial promise in the clinical setting for the treatment of several tumors driven by these oncogenic signaling pathways. Unfortunately, clinical relapse due to acquired resistance to these molecular therapeutics is common. An improved understanding of how tumors bypass the inhibitory effects of RTK-targeted therapies has revealed a rich myriad of possible mechanisms for acquired resistance. Protein tyrosine phosphatases (PTPs) can function as oncogenes or tumor suppressors to either enhance or suppress RTK signaling. Recent studies suggest that the loss or gain of function of PTP's can significantly impinge on RTK signaling during tumor progression. Here we review the interplay between RTKs and PTPs as an emerging mechanism for acquired resistance to RTK-targeted therapies, that may aid in the design of improved therapies to prevent and overcome resistance in treatments for cancer patients.

(A) Prolonged treatment with RTK inhibitors leads to acquired resistance. (B) Gain- or (C) loss-of-function of PTPs may contribute to resistance by activating RTK-independent pathways to promote cancer progression.Figure optionsDownload as PowerPoint slide