Format

Send to

Choose Destination
Bull Math Biol. 2015 Jan;77(1):1-22. doi: 10.1007/s11538-014-0046-4. Epub 2014 Dec 6.

Modeling the effects of space structure and combination therapies on phenotypic heterogeneity and drug resistance in solid tumors.

Author information

1
Sorbonne Universités, UPMC Univ Paris 06, UMR 7598, Laboratoire Jacques-Louis Lions, 75005 , Paris, France, alexander.lorz@upmc.fr.

Abstract

Histopathological evidence supports the idea that the emergence of phenotypic heterogeneity and resistance to cytotoxic drugs can be considered as a process of selection in tumor cell populations. In this framework, can we explain intra-tumor heterogeneity in terms of selection driven by the local cell environment? Can we overcome the emergence of resistance and favor the eradication of cancer cells by using combination therapies? Bearing these questions in mind, we develop a model describing cell dynamics inside a tumor spheroid under the effects of cytotoxic and cytostatic drugs. Cancer cells are assumed to be structured as a population by two real variables standing for space position and the expression level of a phenotype of resistance to cytotoxic drugs. The model takes explicitly into account the dynamics of resources and anticancer drugs as well as their interactions with the cell population under treatment. We analyze the effects of space structure and combination therapies on phenotypic heterogeneity and chemotherapeutic resistance. Furthermore, we study the efficacy of combined therapy protocols based on constant infusion and bang-bang delivery of cytotoxic and cytostatic drugs.

PMID:
25480478
DOI:
10.1007/s11538-014-0046-4
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center