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Deiodinases' Inhibitors: A Double-Edged Sword.

Lucia Acampora1, Caterina Miro1, Annunziata Gaetana Cicatiello1

  • 1Department of Clinical Medicine and Surgery, University of Naples "Federico II", 80131 Naples, Italy.

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|October 11, 2025
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Summary

Deiodinase enzymes regulate thyroid hormone (TH) metabolism and are implicated in cancer. Developing selective deiodinase inhibitors is crucial for cancer therapy, despite challenges in targeting enzyme specificity and tumor heterogeneity.

Keywords:
Thyroid Hormonesdeiodinasesdeiodinases’s inhibitors

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Area of Science:

  • Biochemistry
  • Endocrinology
  • Oncology

Background:

  • Deiodinase enzymes are critical for thyroid hormone (TH) metabolism, activating thyroxine (T4) to triiodothyronine (T3) or inactivating THs.
  • Dysregulation of deiodinases is linked to various diseases, notably cancer, where they influence tumor progression and aggressiveness.
  • Existing inhibitors for deiodinases are limited, posing challenges for therapeutic development.

Purpose of the Study:

  • To provide an overview of current knowledge on deiodinase inhibitors.
  • To highlight the potential and limitations of deiodinase inhibitors, particularly in the context of cancer therapy.
  • To identify future research directions for optimizing deiodinase inhibitor development.

Main Methods:

  • Literature review of deiodinase enzymes and their inhibitors.
  • Analysis of the role of deiodinases in cancer biology and therapeutic implications.
  • Discussion of challenges in achieving enzyme and tissue specificity for inhibitors.

Main Results:

  • Deiodinases play a dual role in cancer, acting as regulators of neoplastic processes with altered expression in tumors.
  • Developing selective deiodinase inhibitors faces hurdles due to enzyme heterogeneity and the need to preserve TH regulation in healthy tissues.
  • Current inhibitors are limited, and significant challenges remain in targeting these enzymes effectively in cancer.

Conclusions:

  • Deiodinase inhibitors show promise as a novel class of cancer therapeutics.
  • Future research must focus on identifying potent inhibitors, improving delivery, and optimizing regimens to balance efficacy and minimize side effects.
  • Addressing the spatial and temporal heterogeneity of deiodinase expression in tumors is key for successful therapeutic strategies.