A Narrative Review of RAS Mutations in Early-Stage Colorectal Cancer: Mechanisms and Clinical Implications
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...
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2025-02-01
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| author | Hasan Cagri Yildirim Damla Gunenc Elvina Almuradova Osman Sutcuoglu Suayib Yalcin |
| author_facet | Hasan Cagri Yildirim Damla Gunenc Elvina Almuradova Osman Sutcuoglu Suayib Yalcin |
| author_sort | Hasan Cagri Yildirim |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-5218b442389e4e75809ad1d12caf5ea2 |
| institution | DOAJ |
| issn | 1010-660X 1648-9144 |
| language | English |
| publishDate | 2025-02-01 |
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| spelling | doaj-art-5218b442389e4e75809ad1d12caf5ea22025-08-20T02:42:22ZengMDPI AGMedicina1010-660X1648-91442025-02-0161340810.3390/medicina61030408A Narrative Review of RAS Mutations in Early-Stage Colorectal Cancer: Mechanisms and Clinical ImplicationsHasan Cagri Yildirim0Damla Gunenc1Elvina Almuradova2Osman Sutcuoglu3Suayib Yalcin4Department of Medical Oncology, Nigde Training and Research Hospital, 51100 Nigde, TurkeyDepartment of Medical Oncology, Ege University Faculty of Medicine, 35040 Izmir, TurkeyMedicana Hospital, 34520 Istanbul, TurkeyDepartment of Medical Oncology, Etlik City Hospital, 06170 Ankara, TurkeyDepartment of Medical Oncology, Hacettepe University Faculty of Medicine, 06230 Ankara, TurkeyColorectal 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.https://www.mdpi.com/1648-9144/61/3/408colon cancerKRAS mutationMSI/MSS statusprognostic markersearly-stagesurvival |
| spellingShingle | Hasan Cagri Yildirim Damla Gunenc Elvina Almuradova Osman Sutcuoglu Suayib Yalcin A Narrative Review of RAS Mutations in Early-Stage Colorectal Cancer: Mechanisms and Clinical Implications Medicina colon cancer KRAS mutation MSI/MSS status prognostic markers early-stage survival |
| title | A Narrative Review of RAS Mutations in Early-Stage Colorectal Cancer: Mechanisms and Clinical Implications |
| title_full | A Narrative Review of RAS Mutations in Early-Stage Colorectal Cancer: Mechanisms and Clinical Implications |
| title_fullStr | A Narrative Review of RAS Mutations in Early-Stage Colorectal Cancer: Mechanisms and Clinical Implications |
| title_full_unstemmed | A Narrative Review of RAS Mutations in Early-Stage Colorectal Cancer: Mechanisms and Clinical Implications |
| title_short | A Narrative Review of RAS Mutations in Early-Stage Colorectal Cancer: Mechanisms and Clinical Implications |
| title_sort | narrative review of ras mutations in early stage colorectal cancer mechanisms and clinical implications |
| topic | colon cancer KRAS mutation MSI/MSS status prognostic markers early-stage survival |
| url | https://www.mdpi.com/1648-9144/61/3/408 |
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