CSCIED

期刊目次

加入编委

期刊订阅

添加您的邮件地址以接收即将发行期刊数据:

Open Access Article

International Journal of Clinical Research. 2023; 7: (9) ; 8-11 ; DOI: 10.12208/j.ijcr.20230311.

Research Progress in targeted therapy for advanced NSCLC with KRAS mutation
KRAS突变晚期NSCLC靶向治疗研究进展

作者: 薛彩花, 韩舒 *, 李鹏涛, 陈士花, 刘巧玲, 刘洪训

黄岛区中心医院肿瘤科 山东青岛

*通讯作者: 韩舒,单位:黄岛区中心医院肿瘤科 山东青岛;

发布时间: 2023-09-30 总浏览量: 461

摘要

肺癌是世界上常见的癌症死亡原因之一,大约85%的肺癌是非小细胞肺癌(non-small cell lung cancer, NSCLC)[1]。KRAS突变在NSCLC驱动基因突变中较为常见[2]。既往针对KRAS突变的NSCLC患者多选择无驱动基因的方案治疗。近年来随着对KRAS突变NSCLC生物学特征的深入研究,KRAS抑制剂临床实验也取得突破性进展[3]。现对KRAS突变晚期NSCLC靶向治疗研究进展作一综述。

关键词: 非小细胞肺癌;KRAS突变;抑制剂

Abstract

Lung cancer is one of the most common causes of cancer death in the world, with approximately 85% of lung cancers being non-small cell lung cancer, NSCLC)[1]. KRAS mutation is relatively common among NSCLC driver gene mutations[2]. In the past, NSCLC patients with KRAS mutation were treated with a non-driver gene regimen. In recent years, with the in-depth research on the biological characteristics of KRAS mutant NSCLC, breakthrough progress has been made in KRAS inhibitor clinical trials[3]. This article reviews the progress of targeted therapy for advanced NSCLC with KRAS mutation.

Key words: Non-small cell lung cancer, NSCLC; KRAS mutation; Inhibitor

参考文献 References

[1] Bravaccini S, Bronte G, Ulivi P.TMB in NSCLC: A Broken Dream?[J] .Int J Mol Sci. 2021 Jun 18;22(12):6536.

[2] Awad MM, Liu S, Rybkin II, et al.Acquired Resistance to KRAS(G12C)Inhibition in Cancer [J].N Engl J Med. 2021 Jun 24;384(25):2382-2393. 

[3] Veluswamy R, Mack PC, Houldsworth J, et al.KRASG12C -Mutant Non-Small Cell Lung Cancer: Biology, Developmental Therapeutics, and Molecular Testing[J].J Mol Diagn. 2021 May;23(5):507-520.

[4] Ferrer I, Zugazagoitia J, Herbertz S,et al. KRAS-Mutant non-small cell lung cancer: From biology to therapy[J]. Lung Cancer. 2018 Oct;124:53-64. 

[5] Kathryn C. Arbour, Emmett Jordan,et al. Effects of Co-occurring Genomic Alterations on Outcomes in Patients with KRAS-Mutant Non–Small Cell Lung Cancer[J].Clin Cancer Res. 2018 Jan 15; 24(2): 334–340. 

[6] Timar J, Kashofer K.Molecular epidemiology and diagnostics of KRAS mutations in human cancer[J].Cancer Metastasis Rev. 2020 Dec;39(4):1029-1038.

[7] 张权,王敬慧,李曦,等.107例KRAS突变阳性非小细胞肺癌患者临床分析[J].中国肺癌杂志,2016, 19(5): 257-262.

[8] 陈会会,李慧,赵晓光,等.KRAS突变非小细胞肺癌患者临床病理特征及预后分析[J].河南医学研究,2021, 30 (9): 1540-1543.

[9] Marabese M, Ganzinelli M, Garassino MC,et al. KRAS mutations affect prognosis of non-small-cell lung cancer patients treated with first-line platinum containing chemotherapy[J].Oncotarget. 2015 Oct 20;6(32):34014-22.

[10] Hong DS, Fakih MG, Strickler JH, et al.KRASG12C Inhibition with Sotorasib in Advanced Solid Tumors[J].N Engl J Med. 2020 Sep 24;383(13):1207-1217.

[11] Linardou H, Kotoula V, Kouvatseas G,et al. Genotyping KRAS and EGFR Mutations in Greek Patients With Non-small-cell Lung Cancer: Incidence, Significance and Implications for Treatment[J].Cancer Genomics Proteo -mics. 2019 Nov-Dec;16(6):531-541.

[12] Skoulidis F, Li BT, Dy GK, et al.Sotorasib for Lung Cancers with KRAS p.G12C Mutation[J].N Engl J Med. 2021 Jun 24;384(25):2371-2381.

[13] Langen AJ, Johnson ML, Mazieres J,et al.Sotorasib versus docetaxel for previously treated non-small-cell lung cancer with KRASG12C mutation: a randomised, open-label, phase 3 trial[J].Lancet. 2023 Mar 4;401(10378):733-746.

[14] Fell JB, Fischer JP, Baer BR, et al. Identification of the Clinical Development Candidate MRTX849, a Covalent KRASG12C Inhibitor for the Treatment of Cancer[J].J Med Chem. 2020 Jul 9;63(13):6679-6693.

[15] Ou SI, Jänne PA, Leal TA, et al.First-in-Human Phase I/IB Dose-Finding Study of Adagrasib (MRTX849) in Patients With Advanced KRASG12C Solid Tumors (KRYSTAL-1)[J].J Clin Oncol. 2022 Feb 15:JCO2102752.

[16] Jänne PA, Riely GJ, Gadgeel SM, et al.Adagrasib in Non-Small-Cell Lung Cancer Harboring a KRASG12C Mutation[J].N Engl J Med. 2022 Jul 14;387(2):120-131.

[17] Weiss A,Lorthiois E,Barys L, et al.Discovery, Preclinical Characterization, and Early Clinical Activity of JDQ443, a Structurally Novel, Potent, and Selective Covalent Oral Inhibitor of KRASG12C[J]. Cancer Discov. 2022 Jun 2;12(6):1500-1517.

[18] Caiola1 E, Frapolli R, Tomanelli M,et al.Wee1 inhibitor MK1775 sensitizes KRAS mutated NSCLC cells to sorafenib[J]. Sci Rep,2018,8(1):948.

[19] Plangger A, Rath B, Stickler S,et al.Cytotoxicity of combinations of the pan‑KRAS SOS1 inhibitor BAY‑293 against pancreatic cancer cell lines[J]. Discov Oncol. 2022 Sep 1;13(1):84.

[20] Jackson M, Ahmari N, Wu J,,et al.Combined KRASG12C and SOS1 inhibition enhances and extends the anti-tumor response in KRASG12C-driven cancers by addressing intrinsic and acquired resistance[J]. J Pharmacol Exp Ther. 2023 May;385(2):106-116.

[21] Hillig RC, Sautier B, Schroeder J,et al.Discovery of potent SOS1 inhibitors that block RAS activation via disruption of the RAS–SOS1 interaction[J].Proc Natl Acad Sci U S A. 2019 Feb 12;116(7):2551-2560.

[22] Hamilton G, Stickler S, Rath B.Targeting of SOS1: from SOS1 Activators to Proteolysis Targeting Chimeras[J].Curr Pharm Des. 2023 Apr 18.

[23] Plangger A, Rath B, Stickler S, et al.Cytotoxicity of combinations of the pan-KRAS inhibitor BAY-293 against primary non-small lung cancer cells[J].Discov Oncol. 2022 Sep 1;13(1):84.

[24] Zhou B, Zang R, Zhang M, et al.Identifying novel tumor-related antigens and immune phenotypes for developing mRNA vaccines in lung adenocarcinoma[J].Int Immuno -pharmacol. 2022 Aug;109:108816. 

[25] Gadgeel SM, Miao J, Riess JW,et al. Phase II study of docetaxel and trametinib in patients with KRAS mutation positive recurrent non-small cell lung cancer (NSCLC) (SWOG S1507, NCT-02642042)[J].Clin Cancer Res. 2023 May 26:CCR-22-3947. 

[26] Jänne PA, Shaw AT, Pereira JR, et al.Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, phase 2 study[J]. Lancet Oncol. 2013 Jan;14(1):38-47.

[27] Jänne PA, van den Heuvel MM, Barlesi F et al.Selumetinib Plus Docetaxel Compared With Docetaxel Alone and Progression-Free Survival in Patients With KRAS-Mutant Advanced Non-Small Cell Lung Cancer: The SELECT-1 Randomized Clinical Trial[J].JAMA. 2017 May 9;317(18): 1844-1853.

引用本文

薛彩花, 韩舒, 李鹏涛, 陈士花, 刘巧玲, 刘洪训, KRAS突变晚期NSCLC靶向治疗研究进展[J]. 国际临床研究杂志, 2023; 7: (9) : 8-11.