1. Dual-specificity phosphatases: therapeutic targets in cancer therapy resistance.
- Author
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Zandi Z, Kashani B, Alishahi Z, Pourbagheri-Sigaroodi A, Esmaeili F, Ghaffari SH, Bashash D, and Momeny M
- Subjects
- Benzofurans pharmacology, Carcinogenesis pathology, Drug Resistance, Neoplasm genetics, Dual Specificity Phosphatase 1 biosynthesis, Dual Specificity Phosphatase 1 genetics, Dual Specificity Phosphatase 6 biosynthesis, Dual Specificity Phosphatase 6 genetics, Gene Expression Regulation, Neoplastic genetics, Humans, Imidazoles pharmacology, JNK Mitogen-Activated Protein Kinases metabolism, Mitogen-Activated Protein Kinase 1 metabolism, Mitogen-Activated Protein Kinase 3 metabolism, Molecular Targeted Therapy methods, Neoplasms pathology, p38 Mitogen-Activated Protein Kinases metabolism, Antineoplastic Agents pharmacology, Dual Specificity Phosphatase 1 antagonists & inhibitors, Dual Specificity Phosphatase 6 antagonists & inhibitors, MAP Kinase Signaling System drug effects, Neoplasms drug therapy
- Abstract
Purpose: Therapy resistance is the principal obstacle to achieving cures in cancer patients and its successful tackling requires a deep understanding of the resistance mediators. Increasing evidence indicates that tumor phosphatases are novel and druggable targets in translational oncology and their modulation may hinder tumor growth and motility and potentiate therapeutic sensitivity in various neoplasms via regulation of various signal transduction pathways. Dual-specificity phosphatases (DUSPs) are key players of cell growth, survival and death and have essential roles in tumor initiation, malignant progression and therapy resistance through regulation of the MAPK signaling pathway. In this review, different aspects of DUSPs are discussed., Methods: A comprehensive literature review was performed using various websites including PubMed., Results: We provide mechanistic insights into the roles of well-known DUSPs in resistance to a wide range of cancer therapeutic approaches including chemotherapy, radiation and molecular targeted therapy in human malignancies. Moreover, we discuss the development of DUSP modulators, with a focus on DUSP1 and 6 inhibitors. Ultimately, the preclinical investigations of small molecule inhibitors of DUSP1 and 6 are outlined., Conclusion: Emerging evidence indicates that the DUSP family is aberrantly expressed in human malignancies and plays critical roles in determining sensitivity to a wide range of cancer therapeutic strategies through regulation of the MAPK signaling pathways. Consequently, targeting DUSPs and their downstream molecules can pave the way for more effective cancer therapies., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2022
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