The Potential Treatment Options and Combination Strategies of KRAS-Mutated Lung Cancer.

IF 2.7 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

OncoTargets and therapy Pub Date : 2024-11-15 eCollection Date: 2024-01-01 DOI:10.2147/OTT.S484209

Xinchao Zhao, Yawen Zheng, Yufeng Wang, Mingyan Zhang, Zhilin Dong, Yanan Liu, Meili Sun

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引用次数: 0

Abstract

In non-small cell lung cancer (NSCLC), Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are found in up to 30% of all cases, with the most prevalent mutations occurring in codons 12 and 13. The development of KRAS-targeted drugs like sotorasib and adagrasib has generated significant excitement in the clinical arena, offering new therapeutic options. Their potential for combination with other treatments broadens the scope for clinical exploration. Acquired resistance to KRAS exon 2 p.G12C inhibitors is a significant challenge, with several reported mechanisms. In this scenario, combination therapy strategies that include targeting Src Homology Region 2 Domain-Containing Phosphatase-2 (SHP2), Son of Sevenless Homolog 1 (SOS1), or downstream effectors of KRAS exon 2 p.G12C are showing promise in overcoming such resistance. However, the efficacy of immune checkpoint inhibitors in this context still requires comprehensive evaluation. The response to anti-Programmed Cell Death Protein 1/Programmed Cell Death Protein 1 Ligand (anti-PD-1/PD-L1) drugs in NSCLC may be significantly influenced by co-occurring mutations, underscoring the need for a personalized approach to treatment based on the specific genetic profile of each tumor.

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KRAS 基因突变肺癌的潜在治疗方案和组合策略。

在非小细胞肺癌（NSCLC）中，有高达 30% 的病例存在 Kirsten 大鼠肉瘤病毒癌基因同源体（KRAS）突变，其中最常见的突变发生在密码子 12 和 13 中。sotorasib 和 adagrasib 等 KRAS 靶向药物的开发为临床提供了新的治疗选择，引起了极大的关注。它们与其他治疗方法联合使用的潜力扩大了临床探索的范围。KRAS外显子2 p.G12C抑制剂的获得性耐药性是一项重大挑战，据报道有多种机制。在这种情况下，包括靶向Src同源区2域含磷酸酶-2（SHP2）、Son of Sevenless Homolog 1（SOS1）或KRAS外显子2 p.G12C下游效应物在内的联合治疗策略有望克服这种耐药性。然而，免疫检查点抑制剂在这种情况下的疗效仍需全面评估。NSCLC患者对抗程序性细胞死亡蛋白1/程序性细胞死亡蛋白1配体（anti-PD-1/PD-L1）药物的反应可能会受到并发突变的显著影响，这突出表明需要根据每种肿瘤的具体遗传特征采取个性化的治疗方法。

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

OncoTargets and therapy BIOTECHNOLOGY & APPLIED MICROBIOLOGY-ONCOLOGY

CiteScore

9.70

自引率

0.00%

发文量

221

审稿时长

1 months

期刊介绍： OncoTargets and Therapy is an international, peer-reviewed journal focusing on molecular aspects of cancer research, that is, the molecular diagnosis of and targeted molecular or precision therapy for all types of cancer. The journal is characterized by the rapid reporting of high-quality original research, basic science, reviews and evaluations, expert opinion and commentary that shed novel insight on a cancer or cancer subtype. Specific topics covered by the journal include: -Novel therapeutic targets and innovative agents -Novel therapeutic regimens for improved benefit and/or decreased side effects -Early stage clinical trials Further considerations when submitting to OncoTargets and Therapy: -Studies containing in vivo animal model data will be considered favorably. -Tissue microarray analyses will not be considered except in cases where they are supported by comprehensive biological studies involving multiple cell lines. -Biomarker association studies will be considered only when validated by comprehensive in vitro data and analysis of human tissue samples. -Studies utilizing publicly available data (e.g. GWAS/TCGA/GEO etc.) should add to the body of knowledge about a specific disease or relevant phenotype and must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Bioinformatics studies must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Single nucleotide polymorphism (SNP) studies will not be considered.