Facilitation of emergence of multidrug-resistant state by alteration of tumor environment: implications from competitive ecology models.

Abstract

The presence of multidrug-resistant (MDR) cells in a solid tumor constitutes a major problem in cancer therapy. Current thinking suggests that the resistant phenotype arises de novo during the tumor's evolution via somatic mutation mechanisms. The proportion of MDR cells, once established, may be enriched during therapy as a consequence of differential cell kill. Michelson et al have developed mathematical models of these phenomena to gain an insight into the dynamics of clonal subpopulation emergence in general and MDR emergence in particular, and I now show that one unexpected consequence of therapy may be the facilitation of MDR emergence due to damage inflicted on the host. The therapeutic damage to the host is modeled as a decreased ability to carry a specific tumor burden.