UniCure: A multi-modal model for predicting personalized cancer therapy response

IF 56.1 1区 医学 Q1 CELL BIOLOGY
Zexi Chen,Saisai Tian,Jiazheng Pei,Ruichu Gu,Yongge Li,Shizhi Ding,Yaqian Xu,Xinlong Zheng,Miaoyu Liu,Xinxing Du,Yuanyuan Zhou,Junchao Zhu,Jiawei Zou,Jing Xu,Wenli Jiang,Chen Ye,Baijun Dong,Qi Zhang,Shengxiang Ren,Shu Wang,Han Wen,Weidong Zhang,Luonan Chen
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引用次数: 0

Abstract

Predicting drug efficacy across diverse patient contexts remains a major challenge in oncology, as models trained on cancer cell lines often fail to capture patient-specific biology. Emerging biological foundation models and patient-derived technologies offer a promising solution. Here, we present UniCure, a multi-modal model that combines biological and chemical foundation models to predict drug-induced transcriptomic responses across diverse cell and tissue contexts, enabling individualized drug ranking. Trained on 1.9 million transcriptomic perturbation profiles spanning >22,000 compounds, 166 cell types, and 24 tissues, UniCure accurately predicts dose-dependent and combination responses and generalizes across bulk and single-cell data. We further fine-tune UniCure on 345 patient-derived tumor-like cluster (PTC) transcriptomic profiles and validate performance on 396 real-world clinical profiles, demonstrating effective patient-level prediction. The model supports response-based patient stratification and is experimentally validated in cell line and patient-derived models. Overall, UniCure provides a practical framework for translating preclinical data into personalized therapeutic strategies.

Abstract Image

UniCure:预测个体化癌症治疗反应的多模态模型
预测不同患者情况下的药物疗效仍然是肿瘤学的一个主要挑战,因为在癌细胞系上训练的模型经常不能捕捉到患者特异性生物学。新兴的生物基础模型和患者衍生的技术提供了一个有希望的解决方案。在这里,我们提出了UniCure,这是一个多模式模型,结合了生物和化学基础模型来预测药物诱导的转录组反应,跨越不同的细胞和组织背景,实现个体化药物排名。UniCure对190万个转录组扰动谱进行了训练,涵盖了22,000种化合物,166种细胞类型和24种组织,可以准确预测剂量依赖性和组合反应,并概括了大量和单细胞数据。我们进一步在345例患者源性肿瘤样簇(PTC)转录组谱上对UniCure进行微调,并在396例真实临床谱上验证其性能,证明了有效的患者水平预测。该模型支持基于反应的患者分层,并在细胞系和患者衍生模型中进行了实验验证。总的来说,UniCure为将临床前数据转化为个性化治疗策略提供了一个实用的框架。
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来源期刊
Cancer Cell
Cancer Cell 医学-肿瘤学
CiteScore
55.20
自引率
1.20%
发文量
179
审稿时长
4-8 weeks
期刊介绍: Cancer Cell is a journal that focuses on promoting major advances in cancer research and oncology. The primary criteria for considering manuscripts are as follows: Major advances: Manuscripts should provide significant advancements in answering important questions related to naturally occurring cancers. Translational research: The journal welcomes translational research, which involves the application of basic scientific findings to human health and clinical practice. Clinical investigations: Cancer Cell is interested in publishing clinical investigations that contribute to establishing new paradigms in the treatment, diagnosis, or prevention of cancers. Insights into cancer biology: The journal values clinical investigations that provide important insights into cancer biology beyond what has been revealed by preclinical studies. Mechanism-based proof-of-principle studies: Cancer Cell encourages the publication of mechanism-based proof-of-principle clinical studies, which demonstrate the feasibility of a specific therapeutic approach or diagnostic test.
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