State-of-the-art and upcoming trends in RAS-directed therapies in gastrointestinal malignancies.

IF 2.8 4区医学 Q2 ONCOLOGY

Current Opinion in Oncology Pub Date : 2024-07-01 Epub Date: 2024-04-19 DOI:10.1097/CCO.0000000000001042

Pieterjan Vanclooster, Sofie Seghers, Hans Prenen

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引用次数: 0

Abstract

Purpose of review: Overall, the review underscores the evolving landscape of KRAS-targeted therapy and the potential for these approaches to improve outcomes for patients with gastrointestinal malignancies. It highlights the importance of ongoing research and clinical trials in advancing precision medicine strategies for KRAS-driven cancers. This review provides a comprehensive overview of the RAS signaling pathway and its significance in gastrointestinal malignancies.

Recent findings: The introduction of KRAS inhibitor represents a significant advancement in the treatment landscape for KRAS-mutant cancers. In this review, we discuss upcoming trends in KRAS-targeted therapy, including the development of mutant-specific direct KRAS inhibitors like MRTX1133 and pan-RAS inhibitors such as RMC-6236. It also explores indirect RAS inhibitors targeting upstream and downstream components of the RAS pathway. Additionally, the review examines other upcoming strategies like combination therapies, such as CDK4/6 and ERK MAPK inhibitors, as well as adoptive cell therapy and cancer vaccines targeting KRAS-mutant cancers.

Summary: Targeting RAS has become an important strategy in treating gastrointestinal cancer. These findings in this review underscore the importance of a multidisciplinary approach, integrating advances in molecular profiling, targeted therapy, immunotherapy, and clinical research to optimize treatment strategies for patients with KRAS-mutant gastrointestinal malignancies.

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胃肠道恶性肿瘤中 RAS 引导疗法的最新进展和未来趋势。

综述的目的：总体而言，这篇综述强调了 KRAS 靶向治疗不断发展的前景，以及这些方法改善胃肠道恶性肿瘤患者预后的潜力。综述强调了正在进行的研究和临床试验在推进针对 KRAS 驱动型癌症的精准医疗策略方面的重要性。本综述全面概述了 RAS 信号通路及其在胃肠道恶性肿瘤中的重要性：KRAS抑制剂的问世标志着KRAS突变癌症治疗领域的重大进展。在这篇综述中，我们讨论了 KRAS 靶向治疗的未来趋势，包括突变体特异性直接 KRAS 抑制剂（如 MRTX1133）和泛 RAS 抑制剂（如 RMC-6236）的开发。报告还探讨了针对 RAS 通路上游和下游成分的间接 RAS 抑制剂。此外，该综述还探讨了其他即将推出的策略，如 CDK4/6 和 ERK MAPK 抑制剂等联合疗法，以及针对 KRAS 突变癌症的收养细胞疗法和癌症疫苗。本综述中的这些发现强调了多学科方法的重要性，这些方法综合了分子剖析、靶向治疗、免疫治疗和临床研究方面的进展，以优化 KRAS 突变胃肠道恶性肿瘤患者的治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current Opinion in Oncology 医学-肿瘤学

CiteScore

6.10

自引率

2.90%

发文量

130

审稿时长

4-8 weeks

期刊介绍： With its easy-to-digest reviews on important advances in world literature, Current Opinion in Oncology offers expert evaluation on a wide range of topics from sixteen key disciplines including sarcomas, cancer biology, melanoma and endocrine tumors. Published bimonthly, each issue covers in detail the most pertinent advances in these fields from the previous year. This is supplemented by annotated references detailing the merits of the most important papers.