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胰腺癌类器官筛选揭示了细胞色素P450 3A5靶向抑制后的个性化敏感性和化疗耐药性抑制。

Pancreatic cancer organoid-screening captures personalized sensitivity and chemoresistance suppression upon cytochrome P450 3A5-targeted inhibition.

作者信息

Cutrona Meritxell B, Wu Jing, Yang Ka, Peng Junmin, Chen Taosheng

机构信息

Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105-3678, USA.

Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105-3678, USA.

出版信息

iScience. 2024 Jun 17;27(7):110289. doi: 10.1016/j.isci.2024.110289. eCollection 2024 Jul 19.

DOI:10.1016/j.isci.2024.110289
PMID:39055940
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11269815/
Abstract

Cytochrome P450 3A5 (CYP3A5) has been proposed as a predictor of therapy response in subtypes of pancreatic ductal adenocarcinoma cancer (PDAC). To validate CYP3A5 as a therapeutic target, we developed a high-content image organoid-based screen to quantify the phenotypic responses to the selective inhibition of CYP3A5 enzymatic activity by clobetasol propionate (CBZ), using a cohort of PDAC-derived organoids (PDACOs). The chemoresistance of PDACOs to a panel of standard-of-care drugs, alone or in combination with CBZ, was investigated. PDACO pharmaco-profiling revealed CBZ to have anti-cancer activity that was dependent on the CYP3A5 level. In addition, CBZ restored chemo-vulnerability to cisplatin in a subset of PDACOs. A correlative proteomic analysis established that CBZ caused the suppression of multiple cancer pathways sustained by or associated with a mutant form of p53. Limiting the active pool of CYP3A5 enables targeted and personalized therapy to suppress pro-oncogenic mechanisms that fuel chemoresistance in some PDAC tumors.

摘要

细胞色素P450 3A5（CYP3A5）已被提出作为胰腺导管腺癌（PDAC）亚型治疗反应的预测指标。为了验证CYP3A5作为治疗靶点，我们开发了一种基于高内涵图像类器官的筛选方法，使用一组源自PDAC的类器官（PDACOs），来量化丙酸氯倍他索（CBZ）对CYP3A5酶活性选择性抑制的表型反应。研究了PDACOs对一组标准护理药物单独或与CBZ联合使用时的化疗耐药性。PDACO药物分析表明，CBZ具有依赖于CYP3A5水平的抗癌活性。此外，CBZ在一部分PDACOs中恢复了对顺铂的化疗敏感性。一项相关蛋白质组分析证实，CBZ导致了由p53突变形式维持或与之相关的多种癌症通路的抑制。限制CYP3A5的活性库能够实现靶向和个性化治疗，以抑制在某些PDAC肿瘤中助长化疗耐药性的促癌机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/121e/11269815/966c63e56da5/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/121e/11269815/37f5963a1aa0/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/121e/11269815/cff69d5343d5/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/121e/11269815/40ec6039c7b8/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/121e/11269815/6c21f5ac1df6/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/121e/11269815/966c63e56da5/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/121e/11269815/37f5963a1aa0/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/121e/11269815/cff69d5343d5/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/121e/11269815/40ec6039c7b8/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/121e/11269815/6c21f5ac1df6/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/121e/11269815/966c63e56da5/gr4.jpg

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3
Drug-repurposing screen on patient-derived organoids identifies therapy-induced vulnerability in KRAS-mutant colon cancer.基于患者来源的类器官的药物重定位筛选鉴定出 KRAS 突变型结肠癌的治疗诱导敏感性。
Cell Rep. 2023 Apr 25;42(4):112324. doi: 10.1016/j.celrep.2023.112324. Epub 2023 Mar 30.
4
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JCO Oncol Pract. 2023 Jan;19(1):19-32. doi: 10.1200/OP.22.00328. Epub 2022 Sep 22.
5
The drug-induced phenotypic landscape of colorectal cancer organoids.药物诱导的结直肠癌细胞类器官表型景观。
Nat Commun. 2022 Jun 6;13(1):3135. doi: 10.1038/s41467-022-30722-9.
6
SynergyFinder 3.0: an interactive analysis and consensus interpretation of multi-drug synergies across multiple samples.SynergyFinder 3.0：一种跨多个样本的多药物协同作用的交互式分析和共识解释。
Nucleic Acids Res. 2022 Jul 5;50(W1):W739-W743. doi: 10.1093/nar/gkac382.
7
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Nat Cancer. 2022 Apr;3(4):418-436. doi: 10.1038/s43018-022-00359-0. Epub 2022 Apr 25.
8
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