Sütcüoğlu Osman, Yıldırım Hasan Çağrı, Almuradova Elvina, Günenç Damla, Yalçın Şuayib
Department of Medical Oncology, Gazi University, Ankara 06560, Turkey.
Department of Medical Oncology, Niğde Research and Training Hospital, Niğde 51100, Turkey.
Medicina (Kaunas). 2025 Jun 30;61(7):1202. doi: 10.3390/medicina61071202.
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.
结直肠癌（CRC）仍然是全球癌症相关死亡的主要原因，带来了重大的治疗挑战，尤其是其转移性形式（mCRC）。本综述全面研究了RAS突变的关键作用，特别是KRAS和NRAS，它们在约40-45%的mCRC病例中被检测到，以及它们对治疗决策和患者预后的影响。我们评估了RAS突变人群中标准治疗的有效性，突出了这些疗法面临的挑战和局限性。靶向治疗的最新进展，特别是对新型药物如KRAS G12C抑制剂（包括索托拉西布和阿达格拉西布）的关注，在克服对传统治疗的耐药性方面显示出有前景的疗效。此外，本综述讨论了未来方向，强调需要研究非RAS靶点以应对耐药机制的复杂性并改善治疗结果。本综述旨在详细概述当前的治疗方法和创新方法，支持为mCRC患者制定个性化管理策略。
