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Dual-specificity phosphatases: therapeutic targets in cancer therapy resistance

Zahra Zandi1, Bahareh Kashani1, Zivar Alishahi1

  • 1Hematology/Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Journal of Cancer Research and Clinical Oncology
|January 4, 2022
PubMed
Abstract

Insights

Dual-specificity phosphatases (DUSPs) are key regulators of cancer therapy resistance by controlling the MAPK pathway. Targeting DUSPs offers a promising strategy to enhance cancer treatment efficacy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Therapy resistance is a major challenge in cancer treatment, necessitating a deeper understanding of resistance mechanisms.
  • Tumor phosphatases are emerging as druggable targets in oncology, with potential to inhibit tumor progression and enhance therapeutic sensitivity.
  • Dual-specificity phosphatases (DUSPs) are critical regulators of cell signaling, impacting tumor initiation, progression, and resistance via the MAPK pathway.

Purpose of the Study:

  • To review the multifaceted roles of DUSPs in cancer therapy resistance.
  • To explore DUSP involvement in resistance to chemotherapy, radiation, and targeted therapies.
  • To discuss the development and preclinical investigation of DUSP modulators, particularly inhibitors of DUSP1 and DUSP6.

Main Methods:

  • A comprehensive literature review was conducted using databases such as PubMed.
  • Mechanistic insights into DUSP roles in various human malignancies were analyzed.
  • Preclinical data on small molecule inhibitors targeting DUSP1 and DUSP6 were examined.

Main Results:

  • DUSPs play significant roles in mediating resistance to diverse cancer therapeutic modalities.
  • DUSP1 and DUSP6 are key targets for therapeutic intervention.
  • Small molecule inhibitors targeting DUSP1 and DUSP6 have shown preclinical promise.

Conclusions:

  • Aberrant DUSP expression in malignancies contributes to therapeutic resistance.
  • DUSPs regulate sensitivity to cancer therapies through MAPK signaling.
  • Targeting DUSPs presents a viable strategy for developing more effective cancer treatments.
Keywords:
Cancer therapy resistanceDUSPSmall molecule DUSP inhibitors

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