Personalized cancer treatment strategies incorporating irreversible and reversible drug resistance mechanisms

作者：Wei He, Matthew McCoy, Rebecca B. Riggins, Robert A. Beckman, Chen-Hsiang Yeang · 发表于：npj Systems Biology and Applications · 年份：2025 · DOI：10.1038/s41540-025-00547-5 · 被引用次数：6 · 研究领域：Cancer Genomics and Diagnostics、Lung Cancer Treatments and Mutations、Cancer Cells and Metastasis

Despite advances in targeted cancer therapy, the promise of precision medicine has been limited by resistance to these treatments. In this study, we propose a mathematical modelling framework incorporating cellular heterogeneity, genetic evolutionary dynamics, and non-genetic plasticity, accounting for both irreversible and reversible drug resistance. Previously we proposed Dynamic Precision Medicine (DPM), a personalized treatment strategy that designed individualized treatment sequences by simulations of irreversible genetic evolutionary dynamics in a heterogeneous tumor. Here we apply DPM to the joint model of reversible and irreversible drug resistance mechanisms, analyze the simulation results and compare the efficacy of various treatment strategies. The results indicate that this enhanced version of DPM significantly outperforms current personalized medicine treatment approaches. Our results provide insights into cancer treatment strategies for heterogeneous tumors with genetic evolutionary dynamics and non-genetic cellular plasticity, potentially leading to improvements in survival time for cancer patients.