Open AccessDosage strategies for delaying resistance emergence in heterogeneous tumors
Author(s) -
Vakil Vahideh,
Trappe Wade
Publication year - 2021
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.13129
Subject(s) - drug resistance , drug , schedule , pharmacodynamics , resistance (ecology) , dosing , pharmacokinetics , medicine , somatic evolution in cancer , cancer , biology , pharmacology , computer science , genetics , ecology , operating system
Drug resistance in cancer treatments is a frequent problem that, when it arises, leads to failure in therapeutic efforts. Tumor heterogeneity is the primary reason for resistance emergence and a precise treatment design that takes heterogeneity into account is required to postpone the rise of resistant subpopulations in the tumor environment. In this paper, we present a mathematical framework involving clonal evolution modeling of drug‐sensitive and drug‐resistant clones. Using our framework, we examine delaying the rise of resistance in heterogeneous tumors during control phase of therapy in a containment treatment approach. We apply pharmacokinetic/pharmacodynamic (PKPD) modeling and show that dosage strategies can be designed to control the resistant subpopulation. Our results show that the drug dosage and schedule determine the relative dynamics of sensitive and resistant clones. We present an optimal control problem that finds the dosing strategy that maximizes the delay in resistance emergence for a given period of containment treatment.