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一种用于从药物筛选中检测治疗诱导抗性的统计框架。

A statistical framework for detecting therapy-induced resistance from drug screens.

作者信息

Wu Chenyu, Gunnarsson Einar Bjarki, Foo Jasmine, Leder Kevin

机构信息

Department of Industrial and Systems Engineering, University of Minnesota, Twin Cities, MN, USA.

Division of Applied Mathematics, Science Institute, University of Iceland, Reykjavik, Iceland.

出版信息

NPJ Syst Biol Appl. 2025 Aug 6;11(1):88. doi: 10.1038/s41540-025-00560-8.

Abstract

Resistance to therapy remains a significant challenge in cancer treatment, often due to the presence of a stem-like cell population that drives tumor recurrence post-treatment. Moreover, many anticancer therapies induce plasticity, converting initially drug-sensitive cells to a more resistant state, e.g. through epigenetic processes and de-differentiation programs. Understanding the balance between therapeutic anti-tumor effects and induced resistance is critical for identifying treatment strategies. In this study, we present a robust statistical framework leveraging multi-type branching process models to characterize the evolutionary dynamics of tumor cell populations. This approach enables the detection and quantification of therapy-induced resistance using high-throughput drug screening data involving total cell counts, without requiring information on subpopulation counts. The framework is validated using both simulated (in silico) and recent experimental (in vitro) datasets, demonstrating its ability to generate meaningful predictions.

摘要

对治疗产生耐药性仍然是癌症治疗中的一个重大挑战,这通常是由于存在一种干细胞样细胞群体,它会导致治疗后肿瘤复发。此外,许多抗癌疗法会诱导细胞可塑性,将最初对药物敏感的细胞转变为更具耐药性的状态,例如通过表观遗传过程和去分化程序。了解治疗抗肿瘤效果与诱导耐药性之间的平衡对于确定治疗策略至关重要。在本研究中,我们提出了一个强大的统计框架,利用多类型分支过程模型来表征肿瘤细胞群体的进化动态。这种方法能够使用涉及总细胞计数的高通量药物筛选数据来检测和量化治疗诱导的耐药性,而无需亚群计数信息。该框架通过模拟(计算机模拟)和近期实验(体外)数据集进行了验证,证明了其生成有意义预测的能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1667/12328638/e32d23df9dc3/41540_2025_560_Fig1_HTML.jpg

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