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非小细胞肺癌中 KRAS 的研究现状。

Current perspectives of KRAS in non-small cell lung cancer.

机构信息

Department of Medicine, University of Chicago, 5841 S Maryland Ave, Chicago, IL 60637. USA.

Section of Hematology/Oncology, Department of Medicine, University of Chicago, 5841 S Maryland Ave, Chicago, IL 60637. USA.

出版信息

Curr Probl Cancer. 2024 Aug;51:101106. doi: 10.1016/j.currproblcancer.2024.101106. Epub 2024 Jun 15.


DOI:10.1016/j.currproblcancer.2024.101106
PMID:38879917
Abstract

NSCLC has a diverse genomic background with mutations in key proto-oncogenic drivers including Kirsten rat sarcoma (KRAS) and epidermal growth factor receptor (EGFR). Roughly 40% of adenocarcinoma harbor Kras activating mutations regardless of smoking history. Most KRAS mutations are located at G12, which include G12C (roughly 40%), G12V (roughly 20%), and G12D (roughly 15%). KRAS mutated NSCLC have higher tumor mutational burden and some have increased PD-1 expression, which has resulted in better responses to immunotherapy than other oncogenes. While initial treatment for metastatic NSCLC still relies on chemo-immunotherapy, directly targeting KRAS has proven to be efficacious in treating patients with KRAS mutated metastatic NSCLC. To date, two G12C inhibitors have been FDA-approved, namely sotorasib and adagrasib. In this review, we summarize the different drug combinations used to target KRAS G12c, upcoming G12D inhibitors and novel therapies targeting KRAS.

摘要

非小细胞肺癌(NSCLC)具有多种基因组背景,包括关键原癌基因驱动突变,如 Kirsten 大鼠肉瘤(KRAS)和表皮生长因子受体(EGFR)。大约 40%的腺癌无论吸烟史如何都携带有 Kras 激活突变。大多数 KRAS 突变位于 G12,包括 G12C(约 40%)、G12V(约 20%)和 G12D(约 15%)。KRAS 突变型 NSCLC 具有更高的肿瘤突变负担,并且一些具有增加的 PD-1 表达,这导致对免疫疗法的反应优于其他致癌基因。虽然转移性 NSCLC 的初始治疗仍依赖于化疗免疫治疗,但直接靶向 KRAS 已被证明对治疗 KRAS 突变型转移性 NSCLC 患者有效。迄今为止,已有两种 G12C 抑制剂获得 FDA 批准,即 sotorasib 和 adagrasib。在这篇综述中,我们总结了用于靶向 KRAS G12c 的不同药物组合、即将推出的 G12D 抑制剂以及针对 KRAS 的新型疗法。

相似文献

[1]
Current perspectives of KRAS in non-small cell lung cancer.

Curr Probl Cancer. 2024-8

[2]
The next-generation KRAS inhibitors…What comes after sotorasib and adagrasib?

Lung Cancer. 2024-8

[3]
Activity and resistance to KRAS inhibitors in non-small cell lung cancer and colorectal cancer.

Biochim Biophys Acta Rev Cancer. 2024-5

[4]
Targeted Therapies for Previously "Undruggable" KRAS-Mutated Non-Small Cell Lung Cancer: A Review of Sotorasib and Adagrasib.

Ann Pharmacother. 2024-6

[5]
Dissecting the clinicopathologic, genomic, and immunophenotypic correlates of KRAS-mutated non-small-cell lung cancer.

Ann Oncol. 2022-10

[6]
Targeting KRAS in Non-Small-Cell Lung Cancer: Current Standards and Developments.

Drugs. 2024-5

[7]
Clinical characteristics of KRAS mutation subtypes in non-small cell lung cancer population in Xinjiang, China, and their impact on the prognosis of immunotherapy.

J Cancer Res Clin Oncol. 2024-9-7

[8]
KRAS G12C-Mutant Non-Small Cell Lung Cancer: Biology, Developmental Therapeutics, and Molecular Testing.

J Mol Diagn. 2021-5

[9]
Sotorasib: a treatment for non-small cell lung cancer with the KRAS G12C mutation.

Drugs Today (Barc). 2022-4

[10]
Editorial: Recent Approval of Sotorasib as the First Targeted Therapy for KRAS G12C-Mutated Advanced Non-Small Cell Lung Cancer (NSCLC).

Med Sci Monit. 2022-11-1

引用本文的文献

[1]
Prognostic Impact of KRAS-TP53 Co-Mutations in Patients with Early-Stage Non-Small Cell Lung Cancer: A Single-Center Retrospective Study.

J Clin Med. 2025-7-19

[2]
Radiogenomics of Stereotactic Radiotherapy: Genetic Mechanisms Underlying Radiosensitivity, Resistance, and Immune Response.

Genes (Basel). 2025-6-24

[3]
[Advances in Immunotherapy of KRAS-mutated Non-small Cell Lung Cancer].

Zhongguo Fei Ai Za Zhi. 2025-5-20

[4]
Twist1-induced suppression of oncogene-induced senescence in non-small cell lung cancer requires the transactivation domain of Twist1.

Neoplasia. 2025-8

[5]
Immunotherapy in advanced, G12C-mutant non-small-cell lung cancer: current strategies and future directions.

Ther Adv Med Oncol. 2025-3-14

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