Integrating Circulating Tumor DNA Dynamics and Sequential Organoid Drug Screening Enhances Breast Cancer Treatment Efficacy.

IF 16.6 1区医学 Q1 ONCOLOGY

Cancer research Pub Date : 2025-09-24 DOI:10.1158/0008-5472.can-25-0608

Jialin Liu,Fang Fang,Weiguang Yuan,Tao Chen,Ji Wang,Xiaping Miao,Yuhuan Meng,Chen Song,Wanchun Tan,Jing An,Abiyasi Nanding,Dalin Li,Youxue Zhang,Yongdong Jiang,Yanbo Chen,Shouping Xu,Guoqiang Zhang,Yanni Song,Hui Li,Yajie Gong,Yuanyuan Yu,Siwei Li,Xingda Zhang,Shilu Zhao,Wenhui Hao,Da Pang,Jun Tian,Shihui Yu,Xianyu Zhang

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引用次数: 0

Abstract

Dynamic changes in circulating tumor DNA (ctDNA) variant allele frequency (VAF) reflect real-time therapeutic efficacy. Timely treatment modification guided by ctDNA VAF may enable precision selection of optimized regimens to counteract evolving resistance in breast cancer. Here, we developed a therapeutic approach integrating ctDNA dynamics with sequential organoid drug screening to optimize breast cancer treatment. Targeted deep sequencing on plasma samples from 71 breast cancer patients revealed that ctDNA clearance correlates with improved disease-free survival. Additionally, analysis of 40 breast cancer organoid models demonstrated the potential of organoid culture supernatants for comprehensive mutation profiling and drug sensitivity testing. Together, these findings suggest that combining ctDNA monitoring with organoid-based drug screening can guide adjustments to treatment strategies, offering a promising solution to optimize patient outcomes.

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结合循环肿瘤DNA动力学和序贯类器官药物筛选提高乳腺癌治疗效果。

循环肿瘤DNA （ctDNA）变异等位基因频率（VAF）的动态变化反映了实时的治疗效果。在ctDNA VAF的指导下，及时修改治疗方案可以精确选择优化方案，以对抗乳腺癌中不断发展的耐药性。在这里，我们开发了一种将ctDNA动力学与序贯类器官药物筛选相结合的治疗方法，以优化乳腺癌治疗。对71名乳腺癌患者血浆样本的靶向深度测序显示，ctDNA清除与改善无病生存率相关。此外，对40例乳腺癌类器官模型的分析表明，类器官培养上清液具有进行全面突变分析和药物敏感性测试的潜力。总之，这些发现表明，将ctDNA监测与基于类器官的药物筛选相结合可以指导治疗策略的调整，为优化患者预后提供了一个有希望的解决方案。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer research 医学-肿瘤学

CiteScore

16.10

自引率

0.90%

发文量

7677

审稿时长

2.5 months

期刊介绍： Cancer Research, published by the American Association for Cancer Research (AACR), is a journal that focuses on impactful original studies, reviews, and opinion pieces relevant to the broad cancer research community. Manuscripts that present conceptual or technological advances leading to insights into cancer biology are particularly sought after. The journal also places emphasis on convergence science, which involves bridging multiple distinct areas of cancer research. With primary subsections including Cancer Biology, Cancer Immunology, Cancer Metabolism and Molecular Mechanisms, Translational Cancer Biology, Cancer Landscapes, and Convergence Science, Cancer Research has a comprehensive scope. It is published twice a month and has one volume per year, with a print ISSN of 0008-5472 and an online ISSN of 1538-7445. Cancer Research is abstracted and/or indexed in various databases and platforms, including BIOSIS Previews (R) Database, MEDLINE, Current Contents/Life Sciences, Current Contents/Clinical Medicine, Science Citation Index, Scopus, and Web of Science.