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CHK1 as a Metabolic and Immunological Regulator: Implications for Cancer Therapy

Maria Franza, Aurora Melfi, Filippo Acconcia, Alessandra di Masi*
Department of Science, Roma Tre University, Rome, Italy
* Corresponding Author: Alessandra di Masi. Email: email
(This article belongs to the Special Issue: Rewiring Metabolism for Cancer Treatment: Emerging Approaches)

Oncology Research https://doi.org/10.32604/or.2026.076509

Received 21 November 2025; Accepted 03 March 2026; Published online 03 April 2026

Abstract

Checkpoint kinase 1 (CHK1), a key regulator of cell cycle checkpoints, plays a central role in the DNA damage response network, serving as a critical mediator that links DNA damage detection to DNA repair mechanisms. In recent years, several other cellular functions of CHK1 have gradually been discovered. As well as monitoring genomic integrity, CHK1 coordinates the timing of DNA replication with the availability of metabolic resources. This prevents unscheduled DNA synthesis from exceeding the cell’s metabolic capacity and causing DNA damage. CHK1 activity also contributes to tumour immune surveillance and the modulation of immune cell infiltration and immune escape mechanisms within the tumour microenvironment. Furthermore, CHK1 is involved in the regulation of differentiation and epigenetics. This perspective on CHK1 provides a strategy foundation for next-generation combinatorial therapies. Indeed, the data presented herein underscores the potential of novel therapeutic strategies that target diverse aspects of tumour biology in a simultaneous manner. Despite the current lack of clinically approved CHK1 inhibitors, the pleiotropic roles of this kinase make it an attractive and promising target for new cancer therapies. The present review aims to analyze the structural and functional aspects of CHK1, with a particular focus on its “non-canonical” functions.

Keywords

Checkpoint kinase 1 (CHK1); metabolism; glycolysis; immunomodulation; cancer therapy; checkpoint inhibition; synthetic lethality; immune evasion

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