利用机理数学建模推进癌症药物开发:弥合理论与实践之间的差距。

IF 2.2 4区 医学 Q3 PHARMACOLOGY & PHARMACY Journal of Pharmacokinetics and Pharmacodynamics Pub Date : 2024-12-01 Epub Date: 2024-06-21 DOI:10.1007/s10928-024-09930-x
Alexander Kulesza, Claire Couty, Paul Lemarre, Craig J Thalhauser, Yanguang Cao
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引用次数: 0

摘要

癌症生长、进展和个体治疗反应的定量预测模型是一个快速发展的领域。来自数学建模、系统生物学、制药业和监管机构的研究人员正在合作开发可应用于药物开发的预测模型,并最终应用于癌症患者的临床管理。建模范式和方法层出不穷,因此要对所有分支学科进行全面回顾具有挑战性。因此,根据需求衡量基本设计方面,权衡不同模型类型的机会和局限性至关重要。在本综述中,我们将讨论癌症模型的三种基本类型:空间结构模型、生态模型和以免疫系统为重点的模型。对于每种类型,我们的目标是说明哪些机制导致了癌症生长和反应的可变性和异质性,从而使新模型的适当结构和复杂性变得更加清晰。我们通过主观收集的文献和示例练习,介绍了三种示范性建模类型各自涉及的主要特征,以促进启发和交流,重点在于提供说教而非详尽的概述。最后,我们对未来的多尺度模型设计进行了设想,以影响肿瘤药物开发中的关键决策。
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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Advancing cancer drug development with mechanistic mathematical modeling: bridging the gap between theory and practice.

Quantitative predictive modeling of cancer growth, progression, and individual response to therapy is a rapidly growing field. Researchers from mathematical modeling, systems biology, pharmaceutical industry, and regulatory bodies, are collaboratively working on predictive models that could be applied for drug development and, ultimately, the clinical management of cancer patients. A plethora of modeling paradigms and approaches have emerged, making it challenging to compile a comprehensive review across all subdisciplines. It is therefore critical to gauge fundamental design aspects against requirements, and weigh opportunities and limitations of the different model types. In this review, we discuss three fundamental types of cancer models: space-structured models, ecological models, and immune system focused models. For each type, it is our goal to illustrate which mechanisms contribute to variability and heterogeneity in cancer growth and response, so that the appropriate architecture and complexity of a new model becomes clearer. We present the main features addressed by each of the three exemplary modeling types through a subjective collection of literature and illustrative exercises to facilitate inspiration and exchange, with a focus on providing a didactic rather than exhaustive overview. We close by imagining a future multi-scale model design to impact critical decisions in oncology drug development.

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来源期刊
CiteScore
4.90
自引率
4.00%
发文量
39
审稿时长
6-12 weeks
期刊介绍: Broadly speaking, the Journal of Pharmacokinetics and Pharmacodynamics covers the area of pharmacometrics. The journal is devoted to illustrating the importance of pharmacokinetics, pharmacodynamics, and pharmacometrics in drug development, clinical care, and the understanding of drug action. The journal publishes on a variety of topics related to pharmacometrics, including, but not limited to, clinical, experimental, and theoretical papers examining the kinetics of drug disposition and effects of drug action in humans, animals, in vitro, or in silico; modeling and simulation methodology, including optimal design; precision medicine; systems pharmacology; and mathematical pharmacology (including computational biology, bioengineering, and biophysics related to pharmacology, pharmacokinetics, orpharmacodynamics). Clinical papers that include population pharmacokinetic-pharmacodynamic relationships are welcome. The journal actively invites and promotes up-and-coming areas of pharmacometric research, such as real-world evidence, quality of life analyses, and artificial intelligence. The Journal of Pharmacokinetics and Pharmacodynamics is an official journal of the International Society of Pharmacometrics.
期刊最新文献
Novel endpoints based on tumor size ratio to support early clinical decision-making in oncology drug-development. Translational pharmacokinetic and pharmacodynamic modelling of the anti-ADAMTS-5 NANOBODY® (M6495) using the neo-epitope ARGS as a biomarker. QSP modeling of a transiently inactivating antibody-drug conjugate highlights benefit of short antibody half life. A PopPBPK-RL approach for precision dosing of benazepril in renal impaired patients. Comparison of the power and type 1 error of total score models for drug effect detection in clinical trials.
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