The role and target potential of protein tyrosine phosphatases in cancer.
Protein tyrosine phosphatases (PTPases) are attractive targets for developing novel cancer therapeutics. Activated via gain-of-function point mutations or overexpression, several PTPases have been identified as critical oncogenic molecules in human malignancies that may be targeted with small chemical inhibitors as a therapeutic strategy. Tumor suppressor PTPases have also been discovered as contributing factors in cancer development that may be targeted via intervention of downstream signaling events for therapeutic purposes. In addition, PTPases have been identified as key negative regulators of cytokines or immune cells. Targeting these negative PTPases may improve the efficacy of cytokine therapy and immunotherapy, which currently have modest response rates and limited survival benefit. Inhibitors of selective PTPases have demonstrated significant preclinical antitumor activity, leading to early-phase clinical trials. Further research and development could lead to PTPase-targeted cancer therapeutics in the near future.
Yi
Taolin
T
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, NB40, 9500 Euclid Avenue, Cleveland, OH 44195, USA. yit@ccf.org
Lindner
Daniel
D
D000970:Antineoplastic Agents / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D020935:MAP Kinase Signaling System; D009369:Neoplasms / Q000201:enzymology / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000502:physiology; D017354:Point Mutation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D010744:Phosphoric Monoester Hydrolases; D017027:Protein Tyrosine Phosphatases