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

Sep 22, 2026

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Checkpoint kinase 1 (CHK1) is a central regulator of cell-cycle checkpoints and the DNA damage response, coordinating DNA damage detection with DNA repair pathways. Beyond genomic integrity maintenance, CHK1 aligns DNA replication timing with cellular metabolic capacity to limit replication stress. CHK1 also shapes tumour immune surveillance by influencing immune infiltration and immune escape in the tumour microenvironment, and regulates differentiation and epigenetic programs, supporting rationale for combinatorial cancer therapies.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages36

Reading Time1 h 31 min

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Abstract

Key words

Introduction

Non-canonical functions and tumour microenvironment

CHK1 Structure and Activation

[http://doi.org/10.32604/or.2026.076509](http://doi.org/10.32604/or.2026.076509) REVIEW CHK1 as a Metabolic and Immunological Regulator: Implications for Cancer Therapy Maria Franza, Aurora Melfi, Filippo Acconcia and Alessandra di Masi* Department of Science, Roma Tre University, Rome, Italy *Corresponding Author: Alessandra di Masi. Email: [alessandra.dimasi@uniroma3.it](alessandra.dimasi@uniroma3.it)[ ](alessandra.dimasi@uniroma3.it)[Received: 21 November 2025](Received: 21 November 2025); [Accepted: 03 March 2026](Accepted: 03 March 2026); [Published: 21 May 2026](Published: 21 May 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 1 Introduction Checkpoint kinase 1 (CHK1) is a pivotal regulator of cell cycle checkpoints and represents a central component of the DNA damage response (DDR) network. CHK1 acts as a critical intermediary integrating signals from DNA damage sensors and orchestrating downstream repair pathways to maintain genomic integrity [1] . CHK1 precisely schedules DNA replication events to match the cell’s metabolic capacity, thereby preventing detrimental replication stress (RS) and avoiding excessive DNA damage caused by unscheduled synthesis [2] . CHK1 kinase activity controls this function, enabling CHK1 to phosphorylate various downstream targets to inhibit origin firing during replication and stabilise replication forks. This maintains genome integrity [3,4] . CHK1 plays an essential role in cell cycle control that is independent of its canonical function in DDR and genome integrity maintenance [5] . CHK1 primarily acts as a safety mechanism blocking proliferating cells during all the cell cycle phases (i.e., G1, S, G2, and mitosis), thus regulating the cellular decision to either progress or stall at specific checkpoints. This ensures that damaged or incompletely replicated DNA Copyright © 2026 The Authors. Published by Tech Science Press. This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. is not passed on to daughter cells. The role of CHK1 in cell cycle progression is physiological, independent of exogenous stress or DNA damage [5,6] . Recent findings have revealed a plethora of non-canonical cellular functions for CHK1 . This kinase has been shown to modulate chromatin structure through histone modifications, which represent an intrinsic cont

FAQs

What core pathways does CHK1 regulate in cells?

CHK1 coordinates the DNA damage response by linking DNA damage detection to downstream repair mechanisms and by maintaining genomic integrity during replication.

How does CHK1 connect metabolism with DNA replication?

CHK1 schedules DNA replication to match cellular metabolic capacity, preventing unscheduled DNA synthesis that could trigger replication stress and additional DNA damage.

How might CHK1 influence cancer immunology and therapy strategies?

CHK1 contributes to tumour immune surveillance and modulates immune infiltration and immune escape within the tumour microenvironment, supporting combinatorial therapeutic concepts that pair CHK1 targeting with other metabolic or immunological agents.

Sep 22, 2026

Uploaded by Stanford