The main goal of treatment regimens for metastasis is to control growth rates, not eradicate all cancer cells. Mathematical models offer methodologies that incorporate high-throughput data with dynamic effects on net growth. The ideal approach would simplify, but not over-simplify, a complex problem into meaningful and manageable estimators that predict the response of a patient to specific treatments. We explore here three fundamental approaches with different assumptions concerning resistance mechanisms in which the cells are categorized into either discrete compartments or described by a continuous range of resistance levels. We argue in favor of modeling resistance as a continuum, and demonstrate how integrating cellular growth rates, density-dependent versus exponential growth, and intratumoral heterogeneity improves predictions concerning the resistance heterogeneity of metastases.
Keywords: cell density; clinical application; mathematical model; metastasis; resistance level; tumor heterogeneity.
Published by Elsevier Ltd.