Checkpoint kinase 1 as a promising target in colorectal cancer management

Abstract

This editorial provides insights into the pivotal role of checkpoint kinase 1 (CHEK1) as both a biomarker and therapeutic target in colorectal cancer (CRC), based on findings from a recent study by Pang et al. Using single-cell RNA sequencing and immunohistochemistry, the study demonstrates significant CHEK1 overexpression in CRC tissues and identifies nitidine chloride as a potent CHEK1 inhibitor that disrupts DNA damage repair pathways. These findings underscore the therapeutic potential of CHEK1 inhibition and highlight the need for further research to address gaps in CRC treatment.

Key Words: Colorectal cancer; Checkpoint kinase 1; Biomarker; Therapeutic target; Single-cell RNA sequencing; Nitidine chloride

Core Tip: This editorial highlights checkpoint kinase 1 (CHEK1) as a novel biomarker and therapeutic target in colorectal cancer (CRC). Pang et al demonstrate significant CHEK1 overexpression in CRC tissues using single-cell RNA sequencing, immunohistochemistry, and tissue microarray analyses. They identify nitidine chloride as a potent CHEK1 inhibitor that disrupts DNA damage repair, impairing tumor progression. These findings emphasize CHEK1's potential for improving CRC diagnosis and treatment while addressing research needs for clinical validation and tumor microenvironment exploration.

INTRODUCTION

Colorectal cancer (CRC) represents a significant global health challenge, marked by high mortality rates and limited therapeutic options, particularly in its metastatic stages[1,2]. Despite advances in immunotherapy and targeted therapies, the response rates remain suboptimal, necessitating novel diagnostic and therapeutic approaches[3-5].

The study by Pang et al[6] published in this issue of the World Journal of Clinical Oncology, addresses these challenges by exploring the role of checkpoint kinase 1 (CHEK1) in CRC. This editorial critically evaluates their findings, emphasizing CHEK1’s potential as a biomarker and therapeutic target.

CHEK1 AS A BIOMARKER IN CRC

The study highlights the biomarker potential of CHEK1 in CRC using cutting-edge techniques and global data analyses. Integrating single-cell RNA sequencing, immunohistochemistry, and tissue microarray analyses, the study reveals significant overexpression of CHEK1 in CRC tissues compared to adjacent non-cancerous tissues. The integration of global datasets further supports the consistent upregulation of CHEK1, positioning it as a promising diagnostic biomarker.

CHEK1’s elevated levels align with its established role in cell cycle regulation and DNA damage response, critical pathways in CRC progression[6-8]. These findings highlight CHEK1’s potential for improving early detection and prognosis in CRC. Furthermore, comparisons with other biomarkers, such as immune checkpoint pathways and cell-cycle regulators, underscore CHEK1’s unique role in CRC biology.

THERAPEUTIC IMPLICATIONS OF CHEK1 INHIBITION

In addition to its diagnostic value, CHEK1 holds significant promise as a therapeutic target. Pang et al[6] identify nitidine chloride (NC) as a potent CHEK1 inhibitor through molecular docking studies, demonstrating its strong biding affinity[9,10].

By inhibiting CHEK1 activity, NC disrupts DNA damage repair pathways, sensitizing tumor cells to genotoxic stress and impairing their survival. CRISPR knockout experiments further confirm CHEK1’s role in promoting CRC cell proliferation[11,12]. These findings underscore the potential of integrating CHEK1 inhibitors into precision oncology frameworks, complementing existing therapeutic strategies. Additionally, this article discusses the potential synergistic effects of CHEK1 inhibition with current CRC treatments, including immunotherapies, to enhance treatment outcomes.

ADDRESSING GAPS IN CRC RESEARCH

While the study by Pang et al[6], provides compelling evidence supporting CHEK1’s role as a biomarker and therapeutic target, it also highlights key limitations, including the reliance on specific dataset and the absence of in vivo validation. Addressing these gaps requires further exploration of CHEK1’s mechanistic role in CRC progression, particularly within the tumor microenvironment (TME)[13-15].

Future research should explore CHEK1’s interactions with immune cells, stromal components, and angiogenesis within the TME. Additionally, the potential combinatory effects of CHEK1 inhibition with immunotherapies or chemotherapies warrant investigation. The critical next step is initiating clinical trials to evaluate CHEK1 inhibitor’s efficacy and safety in CRC treatment[16,17]. Furthermore, adherence to ethical standards in acquiring and using human and animal tissue samples in the studies cited must be explicitly acknowledged to ensure rigor and transparency.

CONCLUSION

Pang et al[6] have significantly contributed to CRC research, positioning CHEK1 as both a biomarker and therapeutic target. Their findings lay the groundwork for innovative diagnostic tools and targeted therapies. As CRC treatment evolves, studies like this advance precision oncology, offering hope for improved patient outcomes and survival rates.