Transfer of Drug Resistance Characteristics Between Cancer Cell Subpopulations: A Study Using Simple Mathematical Models

Bull Math Biol. 2016 Jun;78(6):1218-37. doi: 10.1007/s11538-016-0182-0. Epub 2016 Jun 23.


Resistance to chemotherapy is a major cause of cancer treatment failure. The processes of resistance induction and selection of resistant cells (due to the over-expression 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 well known and has received little attention in the mathematical literature. In this paper, we discuss the potential of simple mathematical models to describe the process of resistance transfer, specifically P-gp transfer, in mixtures of resistant and sensitive tumor cell populations. Two different biological hypotheses for P-gp transfer are explored: (1) exchange through physical cell-cell connections and (2) through microvessicles 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 biological processes involved are discussed on the basis of the results obtained.

Keywords: Inter-cellular transfer; P-glycoprotein; Resistance to chemotherapy.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology
  • Biological Transport, Active
  • Cell Communication / physiology
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell-Derived Microparticles / physiology
  • Drug Resistance, Neoplasm / physiology*
  • Humans
  • Logistic Models
  • Mathematical Concepts
  • Models, Biological*
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Neoplasms / physiopathology


  • ATP Binding Cassette Transporter, Subfamily B, Member 1