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Current Status of PTP-Based Therapeutics

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Protein Tyrosine Phosphatases in Cancer

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Abstract

Protein tyrosine phosphorylation regulates virtually all aspects of cellular function. Proper levels of protein tyrosine phosphorylation are controlled by protein-tyrosine kinases (PTKs) and protein-tyrosine phosphatases (PTPs). Deregulation of tyrosine phosphorylation-mediated signaling is a major cause of cancer. Indeed, PTKs represent an important class of anti-cancer drug targets with more than 20 drugs already approved by the FDA. Several PTPs are also implicated in tumor onset, progression and metastasis, and have attracted attention as potential therapeutic targets for cancer treatment. The most recognized members of the PTP family include PTP1B, SHP2, CDC25, and PRLs. PTP1B plays a positive role in breast cancer progression; SHP2 germ line and somatic gain-of-function mutations cause Noonan Syndrome, juvenile myelomonocytic leukemia, acute myeloid leukemia, and solid tumors; CDC25 regulates cell cycle progression and is overexpressed in a number of human cancers; and the PRLs are overexpressed in cancer and have been linked to tumor metastasis. Hence, inhibitors directed against these PTPs can serve as potential novel anti-cancer agents. This chapter provides an overview of the mechanisms of these oncogenic PTPs in promoting cancer, the approaches for inhibitor discovery, as well as the current status of drug development targeting these phosphatases.

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Acknowledgments

This work was supported in part by National Institutes of Health Grant CA152194.

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  1. Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN, 46202, USA

    Rongjun He & Zhong-Yin Zhang

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Correspondence to Zhong-Yin Zhang .

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  1. Laura and Isaac Perlmutter Cancer Center, NY, New York, USA

    Benjamin G. Neel

  2. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA

    Nicholas K. Tonks

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He, R., Zhang, ZY. (2016). Current Status of PTP-Based Therapeutics. In: Neel, B., Tonks, N. (eds) Protein Tyrosine Phosphatases in Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-3649-6_13

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