Treating KRAS G12C lung cancer: therapeutic potential of investigation drugs in early clinical study.

IF 4.9 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Kendra Wilson, Jesus Salvador Flores Banda, Fatima Raza, Sanjana Bukkapatnam, Sanjana Gangane, Erminia Massarelli
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引用次数: 0

Abstract

Introduction: The KRAS (Kirsten rat sarcoma viral oncogene homolog) gene is recognized as the most frequently mutated oncogene in advanced non-small cell lung cancer (NSCLC). The most prevalent mutation within this gene is G12C, formally known as KRAS G12C, which leads to the substitution of glycine with cysteine at position 12 of the KRAS protein.

Areas covered: Recent advancements in research have developed effective therapies designed to inhibit activated KRAS signaling. As a result, the first two accelerated FDA-approved KRAS inhibitors, sotorasib, and adagrasib have been successfully introduced to the market for locally advanced or metastatic KRAS G12C mutated NSCLC who progressed after prior therapy. A second generation of KRAS inhibitors is currently being tested in clinical trials, and in combination with immunotherapy and chemotherapy.

Expert opinion: Future research is crucial to determine the optimal timing for treatment with KRAS G12C inhibitors. Additional studies are needed to identify biomarkers that predict which patients will benefit most. This review discusses and analyzes both completed and ongoing clinical trials of first and second-generation KRAS inhibitors. It also addresses mechanisms of resistance to KRAS inhibition, potential therapeutic strategies to overcome this resistance, biomarkers, side effects, and its role in central nervous system metastatic disease.

治疗KRAS G12C肺癌:研究药物在早期临床研究中的治疗潜力。
KRAS (Kirsten大鼠肉瘤病毒癌基因同源)基因被认为是晚期非小细胞肺癌(NSCLC)中最常见的突变癌基因。该基因中最常见的突变是G12C,正式名称为KRAS G12C,它导致KRAS蛋白[6]第12位的甘氨酸被半胱氨酸取代。涵盖领域:最近的研究进展已经开发出有效的疗法,旨在抑制活化的KRAS信号。因此,fda批准的前两种加速KRAS抑制剂sotorasib和adagrasib已成功引入市场,用于局部晚期或转移性KRAS g12c突变的NSCLC,这些NSCLC在先前治疗后进展。第二代KRAS抑制剂目前正在临床试验中进行测试,并与免疫疗法和化疗联合使用。专家意见:未来的研究对于确定KRAS G12C抑制剂治疗的最佳时机至关重要。需要进一步的研究来确定生物标志物,以预测哪些患者将受益最大。本综述讨论并分析了第一代和第二代KRAS抑制剂已完成和正在进行的临床试验。它还讨论了对KRAS抑制的耐药性机制,克服这种耐药性的潜在治疗策略,生物标志物,副作用及其在中枢神经系统转移性疾病中的作用。
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来源期刊
CiteScore
10.00
自引率
0.00%
发文量
71
审稿时长
6-12 weeks
期刊介绍: Expert Opinion on Investigational Drugs (ISSN 1354-3784 [print], 1744-7658 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles and original papers on drugs in preclinical and early stage clinical development, providing expert opinion on the scope for future development. The Editors welcome: Reviews covering preclinical through to Phase II data on drugs or drug classes for specific indications, and their potential impact on future treatment strategies Drug Evaluations reviewing the clinical and pharmacological data on a particular drug Original Research papers reporting the results of clinical investigations on agents that are in Phase I and II clinical trials The audience consists of scientists, managers and decision-makers in the pharmaceutical industry, and others closely involved in R&D.
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