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鉴定抗癌药物耐药性小分子抑制剂的方案。

Protocol to identify small-molecule inhibitors against cancer drug resistance.

作者信息

Wei Juan, Zhang She-Yu, Zhou Xue-Yuan, Wei Yong, Jia Hao-Ran, Wu Qin, Tan Weihong

机构信息

School of Science, Tianjin University, Tianjin, China.

School of Life Sciences, Tianjin University, Tianjin, China.

出版信息

STAR Protoc. 2025 Mar 21;6(1):103605. doi: 10.1016/j.xpro.2025.103605. Epub 2025 Jan 30.

DOI:10.1016/j.xpro.2025.103605
PMID:39888719
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11821401/
Abstract

Drug resistance has emerged as a critical challenge in clinical cancer treatment. Here, we present a high-throughput screening protocol to identify therapeutic small-molecule inhibitors against drug-resistant cancer cells. We detail the steps for constructing drug-resistant cell models, executing the chemical screening process, and performing data analysis and validation. This protocol facilitates the rapid identification of therapeutic strategies for different types of drug-resistant cancers and aids in studying mechanisms. For complete details on the use and execution of this protocol, please refer to Zhang et al..

摘要

耐药性已成为临床癌症治疗中的一项关键挑战。在此,我们提出一种高通量筛选方案,以鉴定针对耐药癌细胞的治疗性小分子抑制剂。我们详细介绍了构建耐药细胞模型、进行化学筛选过程以及进行数据分析和验证的步骤。该方案有助于快速确定针对不同类型耐药癌症的治疗策略,并有助于研究其机制。有关该方案使用和执行的完整详细信息,请参考Zhang等人的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4396/11821401/8ed626eb96cc/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4396/11821401/2e2d7ef0dcde/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4396/11821401/79dcd59713ce/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4396/11821401/5cc52400babe/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4396/11821401/03cf2293b742/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4396/11821401/4ceff276a5f5/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4396/11821401/8ed626eb96cc/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4396/11821401/2e2d7ef0dcde/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4396/11821401/79dcd59713ce/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4396/11821401/5cc52400babe/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4396/11821401/03cf2293b742/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4396/11821401/4ceff276a5f5/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4396/11821401/8ed626eb96cc/gr5.jpg

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本文引用的文献

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A chemical screen identifies PRMT5 as a therapeutic vulnerability for paclitaxel-resistant triple-negative breast cancer.一种化学筛选方法确定 PRMT5 是紫杉醇耐药性三阴性乳腺癌的治疗弱点。
Cell Chem Biol. 2024 Nov 21;31(11):1942-1957.e6. doi: 10.1016/j.chembiol.2024.08.003. Epub 2024 Sep 3.
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First-Line Ipatasertib, Atezolizumab, and Taxane Triplet for Metastatic Triple-Negative Breast Cancer: Clinical and Biomarker Results.伊帕替膦联合阿替利珠单抗和紫杉烷类三药方案治疗转移性三阴性乳腺癌的临床和生物标志物结果。
Clin Cancer Res. 2024 Feb 16;30(4):767-778. doi: 10.1158/1078-0432.CCR-23-2084.
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Alteration of chromatin high-order conformation associated with oxaliplatin resistance acquisition in colorectal cancer cells.
与大肠癌细胞中获得性奥沙利铂耐药相关的染色质高级构象改变
Exploration (Beijing). 2023 May 29;3(4):20220136. doi: 10.1002/EXP.20220136. eCollection 2023 Aug.
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Mammalian SWI/SNF chromatin remodeling complexes promote tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer.哺乳动物 SWI/SNF 染色质重塑复合物促进 EGFR 突变型肺癌对酪氨酸激酶抑制剂的耐药性。
Cancer Cell. 2023 Aug 14;41(8):1516-1534.e9. doi: 10.1016/j.ccell.2023.07.005. Epub 2023 Aug 3.
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Mitochondrial adaptation in cancer drug resistance: prevalence, mechanisms, and management.线粒体适应性在癌症耐药中的作用:普遍性、机制与管理。
J Hematol Oncol. 2022 Jul 18;15(1):97. doi: 10.1186/s13045-022-01313-4.
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PRMT inhibition induces a viral mimicry response in triple-negative breast cancer.PRMT 抑制在三阴性乳腺癌中诱导病毒模拟反应。
Nat Chem Biol. 2022 Aug;18(8):821-830. doi: 10.1038/s41589-022-01024-4. Epub 2022 May 16.
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Paclitaxel's Mechanistic and Clinical Effects on Breast Cancer.紫杉醇对乳腺癌的作用机制和临床疗效。
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