Mathematical Modeling of Tumor Immune Interactions: The Role of Anti-FGFR and Anti-PD-1 in the Combination Therapy.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2024-08-07 DOI:10.1007/s11538-024-01329-6
Chenghang Li, Zonghang Ren, Guiyu Yang, Jinzhi Lei
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Abstract

Bladder cancer poses a significant global health burden with high incidence and recurrence rates. This study addresses the therapeutic challenges in advanced bladder cancer, focusing on the competitive mechanisms of ligand or drug binding to receptors. We developed a refined mathematical model that integrates the dynamics of tumor cells and immune responses, particularly targeting fibroblast growth factor receptor 3 (FGFR3) and immune checkpoint inhibitors (ICIs). This study contributes to understanding combination therapies by elucidating the competitive binding dynamics and quantifying the synergistic effects. The findings highlight the importance of personalized immunotherapeutic strategies, considering factors such as drug dosage, dosing schedules, and patient-specific parameters. Our model further reveals that ligand-independent activated-state receptors are the most essential drivers of tumor proliferation. Moreover, we found that PD-L1 expression rate was more important than PD-1 in driving the dynamic evolution of tumor and immune cells. The proposed mathematical model provides a comprehensive framework for unraveling the complexities of combination therapies in advanced bladder cancer. As research progresses, this multidisciplinary approach contributes valuable insights toward optimizing therapeutic strategies and advancing cancer treatment paradigms.

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肿瘤免疫相互作用的数学建模:抗表皮生长因子受体和抗 PD-1 在联合疗法中的作用。
膀胱癌发病率和复发率都很高,给全球健康造成了巨大负担。本研究针对晚期膀胱癌的治疗难题,重点研究配体或药物与受体结合的竞争机制。我们建立了一个精细的数学模型,该模型整合了肿瘤细胞的动态和免疫反应,特别是针对成纤维细胞生长因子受体 3 (FGFR3) 和免疫检查点抑制剂 (ICIs) 的反应。这项研究通过阐明竞争性结合动力学和量化协同效应,有助于理解联合疗法。研究结果强调了个性化免疫治疗策略的重要性,其中考虑到了药物剂量、给药时间表和患者特异性参数等因素。我们的模型进一步揭示了配体依赖性激活状态受体是肿瘤增殖的最基本驱动因素。此外,我们还发现 PD-L1 的表达率比 PD-1 在驱动肿瘤和免疫细胞动态演化方面更为重要。所提出的数学模型为揭示晚期膀胱癌联合疗法的复杂性提供了一个全面的框架。随着研究的深入,这种多学科方法将为优化治疗策略和推进癌症治疗范例提供宝贵的见解。
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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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