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  4. Vol 7, Issue 2, 2026

Research Progress on POLE/POLD1 and Microsatellite Instability in Colorectal Cancer

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DOI: 10.23977/medsc.2026.070209 | Downloads: 0 | Views: 56

Author(s)

Ying Sun 1, Zhaohui Wang 2

Affiliation(s)

1 Dalian Medical University, Dalian, 116000, China
2 Dalian University of Technology Affiliated Central Hospital (Dalian Central Hospital), Dalian, 116000, China

Corresponding Author

Zhaohui Wang

ABSTRACT

Colorectal cancer (CRC), one of the most common malignant tumors in the digestive system, is a heterogeneous disease whose pathogenesis and progression involve a complex interplay of environmental, genetic, and other factors [1]. The 2024 V2 edition of the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Colorectal Cancer underwent comprehensive revision, optimizing multiple dimensions from diagnosis to treatment with a focus on advancements in molecular diagnostic technologies, recent achievements in immunotherapy, and adjustments to multimodal treatment strategies. The guidelines emphasize the need for a comprehensive upgrade in molecular testing for patients with suspected or confirmed metastatic adenocarcinoma. In addition to routine testing for RAS and BRAF gene mutations, HER2 gene amplification, and mismatch repair (MMR)/microsatellite instability (MSI) status, mandatory testing should now include rare gene mutations or fusions such as POLE/POLD1, RET, and NTRK. Regarding treatment strategies, the guidelines explicitly recommend prioritizing immunotherapy for patients harboring POLE/POLD1 mutations or defects in mismatch repair (dMMR)/high microsatellite instability (MSI-H), particularly those with unresectable metastases. Furthermore, the guidelines update that adjuvant chemotherapy postoperatively may have limited potential in improving survival rates for dMMR/MSI-H patients [2]. Thus, the discovery of additional molecular biomarkers offers novel insights and methodologies for the diagnosis, treatment, and prognostic evaluation of colorectal cancer. This review summarizes the functions of POLE/POLD1, its relationship with mismatch repair defects/high microsatellite instability (MSI), and the roles of POLE/POLD1 mutations and MSI in the pathogenesis and progression of colorectal cancer.

KEYWORDS

Colorectal cancer, POLE/POLD1 gene, Microsatellite instability, DNA mismatch repair protein

CITE THIS PAPER

Ying Sun, Zhaohui Wang. Research Progress on POLE/POLD1 and Microsatellite Instability in Colorectal Cancer. MEDS Clinical Medicine (2026). Vol. 7, No.2, 61-70. DOI: http://dx.doi.org/10.23977/medsc.2026.070209.

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