RAS Mutations in Advanced Colorectal Cancer: Mechanisms, Clinical Implications, and Novel Therapeutic Approaches

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality globally, posing significant treatment challenges, particularly in its metastatic form (mCRC). This review comprehensively examines the pivotal role of RAS mutations, specifically KRAS and NRAS, which are detected in approxi...

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Main Authors: Osman Sütcüoğlu, Hasan Çağrı Yıldırım, Elvina Almuradova, Damla Günenç, Şuayib Yalçın
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Medicina
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Online Access:https://www.mdpi.com/1648-9144/61/7/1202
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author Osman Sütcüoğlu
Hasan Çağrı Yıldırım
Elvina Almuradova
Damla Günenç
Şuayib Yalçın
author_facet Osman Sütcüoğlu
Hasan Çağrı Yıldırım
Elvina Almuradova
Damla Günenç
Şuayib Yalçın
author_sort Osman Sütcüoğlu
collection DOAJ
description Colorectal cancer (CRC) remains a leading cause of cancer-related mortality globally, posing significant treatment challenges, particularly in its metastatic form (mCRC). This review comprehensively examines the pivotal role of RAS mutations, specifically KRAS and NRAS, which are detected in approximately 40–45% of mCRC cases, and their impact on treatment decisions and patient outcomes. We assess the effectiveness of standard treatments within the RAS mutant population, highlighting the challenges and limitations these therapies face. Recent advancements in targeted therapies, particularly the focus on novel agents such as KRAS G12C inhibitors, including sotorasib and adagrasib, have shown promising efficacy in overcoming resistance to conventional treatments. Furthermore, this review discusses future directions, emphasizing the need for research into non-RAS targets to address the complexities of resistance mechanisms and improve therapeutic outcomes. This review aims to provide a detailed overview of the current treatments and innovative approaches, supporting the development of personalized management strategies for patients with mCRC.
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publishDate 2025-06-01
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record_format Article
series Medicina
spelling doaj-art-b60f073216384dafb47e3000f3a56cba2025-08-20T03:58:30ZengMDPI AGMedicina1010-660X1648-91442025-06-01617120210.3390/medicina61071202RAS Mutations in Advanced Colorectal Cancer: Mechanisms, Clinical Implications, and Novel Therapeutic ApproachesOsman Sütcüoğlu0Hasan Çağrı Yıldırım1Elvina Almuradova2Damla Günenç3Şuayib Yalçın4Department of Medical Oncology, Gazi University, Ankara 06560, TurkeyDepartment of Medical Oncology, Niğde Research and Training Hospital, Niğde 51100, TurkeyDepartment of Medical Oncology, Medicana International İzmir Hospital, İzmir 35170, TurkeyDepartment of Medical Oncology, Ege University, İzmir 35040, TurkeyDepartment of Medical Oncology, Hacettepe University, Ankara 06230, TurkeyColorectal cancer (CRC) remains a leading cause of cancer-related mortality globally, posing significant treatment challenges, particularly in its metastatic form (mCRC). This review comprehensively examines the pivotal role of RAS mutations, specifically KRAS and NRAS, which are detected in approximately 40–45% of mCRC cases, and their impact on treatment decisions and patient outcomes. We assess the effectiveness of standard treatments within the RAS mutant population, highlighting the challenges and limitations these therapies face. Recent advancements in targeted therapies, particularly the focus on novel agents such as KRAS G12C inhibitors, including sotorasib and adagrasib, have shown promising efficacy in overcoming resistance to conventional treatments. Furthermore, this review discusses future directions, emphasizing the need for research into non-RAS targets to address the complexities of resistance mechanisms and improve therapeutic outcomes. This review aims to provide a detailed overview of the current treatments and innovative approaches, supporting the development of personalized management strategies for patients with mCRC.https://www.mdpi.com/1648-9144/61/7/1202colon cancerRAS mutationmolecular oncologysurvival
spellingShingle Osman Sütcüoğlu
Hasan Çağrı Yıldırım
Elvina Almuradova
Damla Günenç
Şuayib Yalçın
RAS Mutations in Advanced Colorectal Cancer: Mechanisms, Clinical Implications, and Novel Therapeutic Approaches
Medicina
colon cancer
RAS mutation
molecular oncology
survival
title RAS Mutations in Advanced Colorectal Cancer: Mechanisms, Clinical Implications, and Novel Therapeutic Approaches
title_full RAS Mutations in Advanced Colorectal Cancer: Mechanisms, Clinical Implications, and Novel Therapeutic Approaches
title_fullStr RAS Mutations in Advanced Colorectal Cancer: Mechanisms, Clinical Implications, and Novel Therapeutic Approaches
title_full_unstemmed RAS Mutations in Advanced Colorectal Cancer: Mechanisms, Clinical Implications, and Novel Therapeutic Approaches
title_short RAS Mutations in Advanced Colorectal Cancer: Mechanisms, Clinical Implications, and Novel Therapeutic Approaches
title_sort ras mutations in advanced colorectal cancer mechanisms clinical implications and novel therapeutic approaches
topic colon cancer
RAS mutation
molecular oncology
survival
url https://www.mdpi.com/1648-9144/61/7/1202
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AT elvinaalmuradova rasmutationsinadvancedcolorectalcancermechanismsclinicalimplicationsandnoveltherapeuticapproaches
AT damlagunenc rasmutationsinadvancedcolorectalcancermechanismsclinicalimplicationsandnoveltherapeuticapproaches
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