Transfer of drug resistance characteristics between cancer cell subpopulations: A study using simple mathematical models.
M. Rosa Durán, A. Podolski-Renic, A. Álvarez-Arenas, J. Dinic, J. Belmonte-Beitia, M. Pesic, V. M. Pérez-García
Bulletin of Mathematical Biology 78, 1218-1237 (2016)
Resistance to chemotherapy is a major cause for cancer treatment fail- ure. The processes of resistance induction and selection of resistant cells (due to the overexpression of the membrane transporter P-glycoprotein, P-gp) are well documented in the literature and a number of mathematical models have been developed. However, another process of transfer of resistant characteristics is less known and has received little attention in the mathematical literature. In this pa- per we discuss the potential of simple mathematical models to describe the process of resistance transfer, specifically P-gp transfer, in mixtures of resistant and sensi- tive tumor cell populations. Two different biological hypotheses for P-gp transfer are explored: (i) exchange through physical cell-cell connections and (ii) through microvesicles (MVs) released to the culture medium. Two models are developed which fit very well the observed population growth dynamics. The potential and limitations of these simple ‘global’ models to describe the aforementioned biolog- ical processes involved are discussed on the basis of the obtained results.