Dual-specificity phosphatases: therapeutic targets in cancer therapy resistance
Autor: | Zahra Zandi, Bahareh Kashani, Zivar Alishahi, Atieh Pourbagheri-Sigaroodi, Fatemeh Esmaeili, Seyed H. Ghaffari, Davood Bashash, Majid Momeny |
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Rok vydání: | 2022 |
Předmět: |
Mitogen-Activated Protein Kinase 1
Cancer Research Mitogen-Activated Protein Kinase 3 Carcinogenesis MAP Kinase Signaling System Imidazoles JNK Mitogen-Activated Protein Kinases Antineoplastic Agents Dual Specificity Phosphatase 1 General Medicine p38 Mitogen-Activated Protein Kinases Gene Expression Regulation Neoplastic Oncology Drug Resistance Neoplasm Dual Specificity Phosphatase 6 Neoplasms Humans Molecular Targeted Therapy Benzofurans |
Zdroj: | Journal of Cancer Research and Clinical Oncology. 148:57-70 |
ISSN: | 1432-1335 0171-5216 |
Popis: | 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.A comprehensive literature review was performed using various websites including PubMed.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.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. |
Databáze: | OpenAIRE |
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