A Narrative Review of RAS Mutations in Early-Stage Colorectal Cancer: Mechanisms and Clinical Implications
Open accessAbstract
Colorectal cancer (CRC) is the third-most common cancer globally and a leading cause of cancer-related deaths. While the prognostic and predictive roles of RAS mutations in advanced CRC are well-established, their significance in early-stage CRC remains a topic of debate. Studies have been conducted for many years on clinical and pathological parameters that may be associated with RAS mutation, and there are inconsistent results in this regard. Currently, the only biomarker used in early-stage CRC is microsatellite status. KRAS mutations are detected in 40–50% of patients with colorectal cancer. RAS activating mutations cause loss of EGFR regulation by acting on the RAS/RAF/MAPK signaling pathways. In advanced colorectal cancer, these mechanisms cause a decrease in the effectiveness of EGFR inhibitors. However, studies on patients with early-stage colorectal cancer have inconsistent results. This review highlights the prognostic and clinical significance of KRAS mutations in early-stage CRC, particularly in MSS tumors. In the MSS group, KRAS mutations were associated with shorter TTR and OS compared to DWT patients. In contrast, in the MSI-H group, KRAS mutations showed no prognostic effect in TTR and OS. However. KRAS mutations were associated with shorter SAR in both MSI-H and MSS groups of patients. The findings underscore the need for routine molecular profiling, including KRAS and MSI status, to refine risk stratification and guide adjuvant therapy decisions. Further studies are warranted to explore targeted therapeutic approaches for KRAS-mutant CRC in the adjuvant setting.
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RAS mutations in colorectal cancer are implicated in remodeling the tumor microenvironment, promoting angiogenesis, modulating immune infiltration, and enhancing metastatic potential.
“Beyond their effect on signaling, RAS mutations in CRC have been implicated in remodeling the tumor microenvironment, promoting angiogenesis, modulating immune infiltration, and enhancing metastatic potential [6].”
From RAS Mutations in Advanced Colorectal Cancer: Mechanisms, Clinical Implications, and Novel Therapeutic Approaches (2025) · cites this paper as [6]
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Khudeir, J. F., & Tlili, A. (2026) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-026-05545-7
Qureshi, I., Shah, V. P., Botterman, E., Ansari, S., & Shaukat, A. (2026) · Journal of Gastrointestinal Cancer · doi:10.1007/s12029-026-01482-2
Colorectal cancer liver metastases: mechanism and therapy
Liu, S., Ban, L.-X., Zhang, W., Sun, Y., Wang, K., Man, Y., & Zhang, Y. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1861130
KRAS Mutations in Cancers: From Undruggable Dilemma to Precision Medicine
Cai, J., Wu, Y., Jia, X., Yang, L., Yang, W., Lu, W., Huang, Z., Pan, Y., Fei, Z., Ru, J., et al. (2026) · MedComm · doi:10.1002/mco2.71050
- Authors
- Yildirim, H. C., Gunenc, D., Almuradova, E., Sutcuoglu, O., & Yalcin, S.
- Affiliations
- Department of Medical Oncology, Nigde Training and Research Hospital, 51100 Nigde, Turkey
- Department of Medical Oncology, Ege University Faculty of Medicine, 35040 Izmir, Turkey
- Medicana Hospital, 34520 Istanbul, Turkey
- Department of Medical Oncology, Etlik City Hospital, 06170 Ankara, Turkey
- Department of Medical Oncology, Hacettepe University Faculty of Medicine, 06230 Ankara, Turkey
- Venue
- Medicina
- Publisher
- MDPI AG
- Published
- 2025-02-26
- Volume
- 61
- Issue
- 3
- Pages
- 408
- ISSN
- 1010-660X (ISSN-L)
- 1648-9144
- PMC
- PMC11944112
- OpenAlex
- W4407988400
- Cited by
- 10
- References
- 75
- Citations by year
- 2026: 5 · 2025: 5
- FWCI
- 1.17
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Medicina (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Keywords
- RAS mutations, KRAS mutation, early colorectal cancer, microsatellite instability, microsatellite stable tumors, Ras/Raf/MAPK signaling, EGFR inhibitors, prognostic factors, time to recurrence, overall survival, disease-free survival, adjuvant therapy, risk stratification, molecular profiling
- MeSH terms
- Humans, Mutation, Neoplasm Staging, Prognosis, Biomarkers, Tumor, Colorectal Neoplasms, Proto-Oncogene Proteins p21(ras)
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