Dual-specificity Phosphatases: Therapeutic Targets in Cancer Therapy Resistance

Overview

Journal J Cancer Res Clin Oncol

Specialty Oncology

Date 2022 Jan 4

PMID 34981193

Citations 14

Authors

Zahra Zandi

Bahareh Kashani

Zivar Alishahi

Atieh Pourbagheri-Sigaroodi

Fatemeh Esmaeili

Seyed H Ghaffari

Davood Bashash

Majid Momeny

Affiliations

Soon will be listed here.

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.

Citing Articles

DUSP12 promotes cell cycle progression and protects cells from cell death by regulating ZPR9.

Abdusamad M, Guo X, Ramirez I, Velasquez E, Cohn W, Gholkar A bioRxiv. 2025; .

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Dynamic and structural insights into allosteric regulation on MKP5 a dual-specificity phosphatase.

Skeens E, Maschietto F, Manjula R, Shillingford S, Lolis E, Batista V bioRxiv. 2024; .

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Upregulation of hsa-miR-141-3p promotes uterine cervical carcinoma progression via targeting dual-specificity protein phosphatase 1.

Liang Z, Zhang W, Zeng D, Chen J, Luo J, Shi L Funct Integr Genomics. 2024; 24(4):137.

PMID: 39138666 DOI: 10.1007/s10142-024-01413-z.

Mechanism and application of feedback loops formed by mechanotransduction and histone modifications.

Sun H, Gao Y, Ma X, Deng Y, Bi L, Li L Genes Dis. 2024; 11(5):101061.

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Aging-associated Alterations in the Gene Regulatory Network Landscape Associate with Risk, Prognosis and Response to Therapy in Lung Adenocarcinoma.

Saha E, Ben Guebila M, Fanfani V, Shutta K, DeMeo D, Quackenbush J bioRxiv. 2024; .

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