A Model of Intratumor and Interpatient Heterogeneity Explains Clinical Trials of Curative Combination Therapy for Lymphoma.

IF 11.5 Q1 HEMATOLOGY

Blood Cancer Discovery Pub Date : 2025-05-05 DOI:10.1158/2643-3230.BCD-24-0230

Amy E Pomeroy, Adam C Palmer

引用次数: 0

Abstract

Significance: A new model of intratumor and interpatient heterogeneity in response to drug combinations explains and predicts the results of clinical trials of curative-intent treatments for DLBCL. This model can be used to understand and inform optimal design of curative drug combinations and clinical trials. See related commentary by Goldstein et al., p. 153.

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肿瘤内和患者间异质性模型解释了淋巴瘤根治性联合疗法的临床试验。

肿瘤药物反应模型已经阐明了肿瘤学中的重要概念，但仍然需要结合肿瘤内和患者间异质性的理论来解释患者的结果，特别是治疗性治疗。我们提出了一个多药物治疗的数学模型，该模型描述了细胞间和患者间药物敏感性分布的异质性，并将其应用于模拟弥漫性大b细胞淋巴瘤（DLBCL）的治疗性联合治疗。模拟试验再现了标准治疗下观察到的无进展生存期和循环肿瘤DNA的变化，并根据药物对复发/难治性DLBCL的疗效准确预测了9项一线联合随机试验的成功或失败。最后，我们使用该模型来探索药物协同作用、生物标志物和亚型特异性终点如何提高靶向联合治疗成功的机会。这项研究提供了一个治疗药物组合的定量模型，并表明预测模拟可以帮助设计具有治疗意图的新方案。

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

Blood Cancer Discovery Multiple-

CiteScore

12.70

自引率

1.80%

发文量

139

期刊介绍： The journal Blood Cancer Discovery publishes high-quality Research Articles and Briefs that focus on major advances in basic, translational, and clinical research of leukemia, lymphoma, myeloma, and associated diseases. The topics covered include molecular and cellular features of pathogenesis, therapy response and relapse, transcriptional circuits, stem cells, differentiation, microenvironment, metabolism, immunity, mutagenesis, and clonal evolution. These subjects are investigated in both animal disease models and high-dimensional clinical data landscapes. The journal also welcomes submissions on new pharmacological, biological, and living cell therapies, as well as new diagnostic tools. They are interested in prognostic, diagnostic, and pharmacodynamic biomarkers, and computational and machine learning approaches to personalized medicine. The scope of submissions ranges from preclinical proof of concept to clinical trials and real-world evidence. Blood Cancer Discovery serves as a forum for diverse ideas that shape future research directions in hematooncology. In addition to Research Articles and Briefs, the journal also publishes Reviews, Perspectives, and Commentaries on topics of broad interest in the field.