Oncogenic Tyrosine Phosphatases: Novel Therapeutic Targets for Melanoma Treatment

Abstract

Despite a large number of therapeutic options available, malignant melanoma remains a highly fatal disease, especially in its metastatic forms. The oncogenic role of protein tyrosine phosphatases (PTPs) is becoming increasingly clear, paving the way for novel antitumor treatments based on their inhibition. In this review, we present the oncogenic PTPs contributing to melanoma progression and we provide, where available, a description of new inhibitory strategies designed against these enzymes and possibly useful in melanoma treatment. Considering the relevance of the immune infiltrate in supporting melanoma progression, we also focus on the role of PTPs in modulating immune cell activity, identifying interesting therapeutic options that may support the currently applied immunomodulating approaches. Collectively, this information highlights the value of going further in the development of new strategies targeting oncogenic PTPs to improve the efficacy of melanoma treatment.

The Low-Molecular Weight Protein Arginine Phosphatase PtpB Affects Nuclease Production, Cell Wall Integrity, and Uptake Rates of Staphylococcus aureus by Polymorphonuclear Leukocytes

“…Our findings, presented here and elsewhere [8], demonstrate that the deletion of ptpB in the clinical S. aureus isolate SA564 alters the transcription of various genes/operons whose products are involved in stress adaptation and infectivity, suggesting that PtpB-driven removal of phosphates from arginine phosphosites is another posttranscriptional mechanism utilized by this pathogen to fine-tune the expression and activity of its virulon, in order to successfully adapt to the diverse host environmental conditions encountered by the bacterium during infection. Given the clear impact of PtpB on the transcription of specific virulence determinants shown here, its impact on S. aureus to cause disease in mice [8], and the fact that several low molecular weight protein tyrosine phosphatase inhibitors are currently in development to combat diseases such as cancer, diabetes/obesity, and bacterial infections [41][42][43][44][45], PtpB might constitute an additional interesting target for drug development against this notorious human nosocomial pathogen.…”

Pan-cancer analyses of classical protein tyrosine phosphatases and phosphatase-targeted therapy in cancer

“…Classical PTPs have been reported to play a role in tumorigenesis and be designed as a drug target for cancer therapy ( 52 , 53 ). Learning in-depth about the molecular characterization and clinical relevance of classical PTPs is conducive to understanding cancer biology and improving clinical treatment.…”

A Plasmodium falciparum protein tyrosine phosphatase inhibitor identified from the ChEMBL‐NTD database blocks parasite growth

“…Dysregulation of protein phosphorylation or alterations in phosphorylation patterns is a primary cause of many human diseases such as cancers, diabetes, autoimmune disorders, and neurological disorders [13,14,[18][19][20]. Kinases and phosphatases are fast emerging as novel drugable targets for many diseases, including diseases caused by various pathogens such as Plasmodium [13,14,[18][19][20][21]38]. We have carried out genome-wise phosphatome analysis of P. falciparum genome previously and identified four tyrosine phosphatases in the genome [10].…”