Background KRAS mutations in metastatic colorectal cancer (mCRC) define a subset of tumors that have primary resistance to anti-EGFR-based therapy. Data concerning whether different KRAS mutations may also have a prognostic value are lacking. Furthermore, novel KRAS G12C inhibitors are currently in development. The aim of our analysis was to compare response rates in patients treated with ...

2025年1月29日 · Historically, KRAS mutations were deemed undruggable. However, in 2022, the US Food and Drug Administration granted breakthrough therapy designation to adagrasib (MRTX849) for the treatment of KRAS-G12C –mutated non–small cell lung cancer.

KRAS突变 是 非小细胞肺癌（NSCLC） 中较常见的驱动基因，中国NSCLC中KRAS突变的发生率约为 10%。 NSCLC中，最常见的KRAS突变亚型为 G12C，约占KRAS突变的 30%，非G12C突变约70%。

2023年8月7日 · 2021年，FDA批准了 安进公司 的AMG510--第一个针对KRAS-G12C突变的直接抑制剂，其表现出肿瘤消退、生存期延长和低脱靶活性。 2022年，FDA批准了MRTX849。 图1. RAS信号通路及相应肿瘤治疗策略 [1] KRAS的结构、信号通路及功能. 图2. KRAS的结构. KRAS基因编码的蛋白相对分子质量为21000，也称为P21蛋白。 Ras 蛋白是小 GTPase 超家族的成员，可以与不活跃的GDP 或活跃的GTP 结合控制细胞内的 信号转导通路。

2025年1月13日 · Targeting KRAS has been a significant challenge in cancer therapy due to its structure, which lacks easily druggable pockets, making it difficult for conventional small molecules to bind effectively. However, recent advances have led to the development of inhibitors that specifically target KRAS G12C inhibitors (Sotorasib and Adagrasib) [31, 32].

2021年9月1日 · Today, Amgen and Mirati Therapeutics have developed two direct KRAS-G12C inhibitors, namely sotorasib (also known as AMG 510 or Lumakras) and adagrasib (also known as MRTX849), which act by ...

2021年11月15日 · Excitingly, AMG510 was the first drug-targeting KRAS (G12C) to be approved for clinical use this year. This review summarises the most recent understanding of fundamental aspects...

2023年10月1日 · KRAS G12C is the most common KRAS variant at ∼13% of NSCLC cases overall. Approved RAS GTPase inhibitors transform KRASG12C into a predictive biomarker. Real-world studies show significant geographic variation in KRAS G12C prevalence. Prospective studies required to ascertain significance of co-mutations (STK11 / KEAP1)

2020年11月12日 · Recent advances in medicinal chemistry have established inhibitors targeting KRAS (G12C), a mutation found in ∼13% of lung adenocarcinomas and, at a lower frequency, in other cancers.

A better understanding of the role of KRAS and its different mutations has led to the development of specific small-molecule inhibitors able to target KRAS G12C, an oncogenic driver mutation in a number of cancers, including non-small cell lung ...