联合药物可以增强其临床疗效，但可能的组合数量和肿瘤间异质性使得确定有效的组合具有挑战性，而现有方法往往忽视临床相关活性。我们筛选了最大的细胞系组之一 (N = 757)，其中包含 51 种临床相关组合，并确定单个细胞系和组织群体水平的反应。我们建立了三种反应类别来模拟单一疗法之外的细胞效应：协同作用、Bliss 相加性和独立药物作用 (IDA)。协同作用很少见（占响应的 11%），但经常有效（活力降低 >50%），而 Bliss 和 IDA 更常见，但有效的频率较低。我们引入“有效的组合效益”（ECB）来描述分类为协同、Bliss 或 IDA 的高效反应。我们在体外鉴定了 ECB 生物标志物，并表明 ECB 比单独的协同作用更好地预测患者来源的异种移植物的反应。我们在这里的工作为临床前评估和联合治疗的开发提供了宝贵的资源和框架。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

Combining drugs can enhance their clinical efficacy, but the number of possible combinations and inter-tumor heterogeneity make identifying effective combinations challenging, while existing approaches often overlook clinically relevant activity. We screen one of the largest cell line panels (N = 757) with 51 clinically relevant combinations and identify responses at the level of individual cell lines and tissue populations. We establish three response classes to model cellular effects beyond monotherapy: synergy, Bliss additivity, and independent drug action (IDA). Synergy is rare (11% of responses) and frequently efficacious (>50% viability reduction), whereas Bliss and IDA are more frequent but less frequently efficacious. We introduce "efficacious combination benefit" (ECB) to describe high-efficacy responses classified as either synergy, Bliss, or IDA. We identify ECB biomarkers in vitro and show that ECB predicts response in patient-derived xenografts better than synergy alone. Our work here provides a valuable resource and framework for preclinical evaluation and the development of combination treatments.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.