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针对 ALK 耐药突变的治疗。

Targeting drug-resistant mutations in ALK.

机构信息

Department of Oncological Sciences, The Tisch Cancer Institute, Mount Sinai Centre for Therapeutic Discovery, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Department of Pharmacological Sciences, The Tisch Cancer Institute, Mount Sinai Centre for Therapeutic Discovery, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

出版信息

Nat Cancer. 2022 Jun;3(6):659-661. doi: 10.1038/s43018-022-00390-1.

DOI:10.1038/s43018-022-00390-1
PMID:35726064
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9919885/
Abstract

Therapy resistance limits the clinical success of tyrosine kinase inhibitors (TKIs) in ALK-positive non-small cell lung cancer. A study now proposes a framework to identify compound resistance mutations to the lorlatinib TKI and provides structure-based drug design approaches to overcome resistance mediated by ALK(G1202R) or ALK(I1171N/S/T).

摘要

治疗耐药性限制了 ALK 阳性非小细胞肺癌酪氨酸激酶抑制剂 (TKI) 的临床疗效。一项研究提出了一种鉴定洛拉替尼 TKI 复合耐药突变的框架，并提供了基于结构的药物设计方法来克服由 ALK(G1202R) 或 ALK(I1171N/S/T) 介导的耐药性。

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Targeting drug-resistant mutations in ALK.针对 ALK 耐药突变的治疗。
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2
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Curr Treat Options Oncol. 2018 May 28;19(7):37. doi: 10.1007/s11864-018-0553-x.
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, a novel rearrangement in lung squamous cell carcinoma and its clinical responses to ALK inhibitors.肺鳞状细胞癌中的一种新型重排及其对ALK抑制剂的临床反应。
J Thorac Dis. 2025 Jan 24;17(1):93-108. doi: 10.21037/jtd-24-1428. Epub 2025 Jan 21.
3
ALK-rearranged and EGFR wild-type lung adenocarcinoma transformed to small cell lung cancer: a case report.ALK重排且表皮生长因子受体野生型肺腺癌转化为小细胞肺癌：一例报告
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本文引用的文献

1
Kinase drug discovery 20 years after imatinib: progress and future directions.伊马替尼发现 20 年后的激酶药物研发：进展与未来方向
Nat Rev Drug Discov. 2021 Jul;20(7):551-569. doi: 10.1038/s41573-021-00195-4. Epub 2021 May 17.
2
Lorlatinib for the treatment of -positive metastatic non-small cell lung cancer.洛拉替尼治疗阳性转移性非小细胞肺癌。
Expert Rev Anticancer Ther. 2020 Apr;20(4):233-240. doi: 10.1080/14737140.2020.1744438. Epub 2020 Mar 25.
3
Sequential ALK Inhibitors Can Select for Lorlatinib-Resistant Compound Mutations in ALK-Positive Lung Cancer.序贯 ALK 抑制剂可选择 ALK 阳性肺癌中 lorlatinib 耐药的复合突变。
Cancer Discov. 2018 Jun;8(6):714-729. doi: 10.1158/2159-8290.CD-17-1256. Epub 2018 Apr 12.
4
EML4-ALK Variants: Biological and Molecular Properties, and the Implications for Patients.EML4-ALK 变体：生物学和分子特性及其对患者的影响
Cancers (Basel). 2017 Sep 5;9(9):118. doi: 10.3390/cancers9090118.
5
Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study.全球、区域和国家癌症发病率、死亡率、生命损失年数、失能生存年数以及 32 种癌症组别的伤残调整生命年数，1990 年至 2015 年：全球疾病负担研究的系统分析。
JAMA Oncol. 2017 Apr 1;3(4):524-548. doi: 10.1001/jamaoncol.2016.5688.
6
Crizotinib resistance: implications for therapeutic strategies.克唑替尼耐药性：对治疗策略的影响。
Ann Oncol. 2016 Sep;27 Suppl 3(Suppl 3):iii42-iii50. doi: 10.1093/annonc/mdw305.
7
Molecular Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in ALK-Rearranged Lung Cancer.ALK 重排肺癌对第一代和第二代 ALK 抑制剂耐药的分子机制
Cancer Discov. 2016 Oct;6(10):1118-1133. doi: 10.1158/2159-8290.CD-16-0596. Epub 2016 Jul 18.
8
ALK mutations confer differential oncogenic activation and sensitivity to ALK inhibition therapy in neuroblastoma.ALK突变在神经母细胞瘤中赋予不同的致癌激活作用以及对ALK抑制疗法的敏感性。
Cancer Cell. 2014 Nov 10;26(5):682-94. doi: 10.1016/j.ccell.2014.09.019.
9
AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer.AZD9291是一种不可逆的表皮生长因子受体酪氨酸激酶抑制剂（EGFR TKI），可克服T790M介导的肺癌对EGFR抑制剂的耐药性。
Cancer Discov. 2014 Sep;4(9):1046-61. doi: 10.1158/2159-8290.CD-14-0337. Epub 2014 Jun 3.
10
Genetic alterations defining NSCLC subtypes and their therapeutic implications.定义 NSCLC 亚型的遗传改变及其治疗意义。
Lung Cancer. 2013 Nov;82(2):179-89. doi: 10.1016/j.lungcan.2013.07.025. Epub 2013 Aug 20.