Abstract
BackgroundDrug-induced resistance is one the major obstacles that may lead to therapeutic failure during cancer treatment. Different genetic alterations occur when tumor cells divide. Among new generations of tumor cells, some may express intrinsic resistance to a specific chemotherapeutic agent. Also, some tumor cells may carry a gene that can develop resistance induced by the therapeutic drug. The methods by which the therapeutic approaches need to be revised in the occurrence of drug induced resistance is still being explored. Previously, we introduced a model that expresses only intrinsic drug resistance in a conjoint normal-tumor cell setting. The focus of this work is to expand our previously reported model to include terms that can express both intrinsic drug resistance and drug-induced resistance. Additionally, we assess the response of the cell population as a function of time under different treatment strategies and discuss the outcomes.MethodsThe model introduced is expressed in the format of coupled differential equations which describe the growth pattern of the cells. The dynamic of the cell populations is simulated under different treatment cases. All computational simulations were executed using Mathematica v7.0.ResultsThe outcome of the simulations clearly demonstrates that while some therapeutic strategies can overcome or control the intrinsic drug resistance, they may not be effective, and are even to some extent damaging, if the administered drug creates resistance by itself.ConclusionIn the present study, the evolution of the cells in a conjoint setting, when the system expresses both intrinsic and induced resistance, is mathematically modeled. Followed by a set of computer simulations, the different growing patterns that can be created based on choices of therapy were examined. The model can still be improved by considering other factors including, but not limited to, the nature of the cancer growth, the level of toxicity that the body can tolerate, or the strength of the patient’s immune system.
Highlights
Drug-induced resistance is one the major obstacles that may lead to therapeutic failure during cancer treatment
The mechanism under which different types of cancers progress is complex. This progression depends on many factors including, but not limited to, the growth rate of cells, mutual interaction of cancer cells with surrounding normal cells, the way in which they are affected by immune system, and their response to anti-cancer treatment
Some of the factors that can contribute to the creation of drug resistance are related to the drug delivery defects, insufficient drug activation at the tumor site, or the resistance that results from genetic mutation of the tumor cells [2, 3]
Summary
Drug-induced resistance is one the major obstacles that may lead to therapeutic failure during cancer treatment. We introduced a model that expresses only intrinsic drug resistance in a conjoint normal-tumor cell setting. The mechanism under which different types of cancers progress is complex This progression depends on many factors including, but not limited to, the growth rate of cells, mutual interaction of cancer cells with surrounding normal cells, the way in which they are affected by immune system, and their response to anti-cancer treatment. Given the importance of implementing the best therapeutic strategy, detecting any pre-existing drug resistance, or any resistance induced by the drug during a course of chemotherapy, is important as it provides insight into the way in which the chemotherapeutic approach needs to be modified [4]
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