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晚期非小细胞肺癌中 K-RAS G12C 抑制剂的最新综述。

An updated overview of K-RAS G12C inhibitors in advanced stage non-small cell lung cancer.

机构信息

Hacettepe University School of Medicine, Ankara, Turkey.

Ankara Bilkent City Hospital, Department of Medical Oncology, Ankara, Turkey.

出版信息

Future Oncol. 2024;20(37):3019-3038. doi: 10.1080/14796694.2024.2407280. Epub 2024 Oct 3.

Abstract

The discovery of mutations, particularly the KRASG12C variant, has been a milestone in understanding the molecular underpinnings of non-small cell lung cancer (NSCLC). These mutations are associated with aggressive tumor behavior and resistance to conventional therapies, highlighting the urgent need for targeted interventions. In this comprehensive review, we analyze the advancements in KRAS G12C inhibitors for the treatment of non-small cell lung cancer. Literature search is made from PubMed, Medline ASCO and ESMO Annual Meetings abstracts by using the following search keywords: "sotorasib", "adagrasib", "divarasib" and "KRAS G12C inhibitors." The last search was on 5 June 2024. This review highlights the importance of pharmacokinetics, pharmacodynamics and potential adverse effects for treating individual patients and ensuring the best outcomes. Additionally, the review discusses research identifying biomarkers that can predict therapy responses and mentions the combination strategies to overcome resistance. Results of the studies and ongoing clinical trials are also briefly summarized in this review. KRASG12C inhibitors sotorasib, adagrasib and the newer divarasib, has revolutionized treating patients harboring this mutation. Ongoing studies and future clinical trials will refine our understandings with the ultimate goal of improving survival and quality of life for patients with this challenging disease.

摘要

突变的发现,特别是 KRASG12C 变异,是理解非小细胞肺癌(NSCLC)分子基础的一个里程碑。这些突变与侵袭性肿瘤行为和对传统疗法的耐药性有关,突出了靶向干预的迫切需要。在这篇全面的综述中,我们分析了 KRAS G12C 抑制剂在治疗非小细胞肺癌方面的进展。通过使用以下搜索关键词,从 PubMed、Medline ASCO 和 ESMO 年会摘要中进行文献检索:“sotorasib”、“adagrasib”、“divarasib”和“KRAS G12C 抑制剂”。最后一次搜索是在 2024 年 6 月 5 日。这篇综述强调了了解药代动力学、药效学和潜在不良反应对于治疗个别患者并确保最佳结果的重要性。此外,该综述还讨论了识别预测治疗反应的生物标志物的研究,并提到了克服耐药性的联合策略。在这篇综述中还简要总结了研究结果和正在进行的临床试验。KRASG12C 抑制剂 sotorasib、adagrasib 和较新的 divarasib,彻底改变了治疗携带这种突变的患者的方法。正在进行的研究和未来的临床试验将进一步加深我们的理解,最终目标是改善患有这种挑战性疾病的患者的生存和生活质量。

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