A Comprehensive Model to Differentiate Spontaneous, Drug-induced, and CSCs-related Drug Resistance

Abstract

AbstractDrug resistance is a pivotal research area in oncology research, yet the integration of multiple sources of resistance into the evolution of drug resistance remains elusive. This study investigates dynamics of drug resistance in chemotherapy utilizing a mathematical model given a treatment protocol. The model categorizes drug resistance into spontaneous, drug-induced, and cancer stem cells (CSCs)-related types. Introducing a novel mathematical framework, this study incorporates explicit dosage-dependent terms to design tailored treatment strategies. A comparative analysis contrasts continuous constant therapy with periodic bolus injection. Virtual patients’ survival times are assessed under baseline dosages for both therapies, revealing the interplay between constant dosage in continuous therapy and maximum dosage in bolus injection on survival time. Our findings demonstrate that, at equivalent cumulative dosages, bolus injection markedly extends patient survival. Furthermore, a potentially bimodal relationship emerges between bolus injection efficacy and maximum dosage, suggesting that two optimal bolus injection strategies may hold.