  Cell competition is recognized to be instrumental to the dynamics and
structure of the tumor-host interface in invasive cancers. In mild competition
scenarios, the healthy tissue and cancer cells can coexist. When the
competition is aggressive, competitive cells, the so called super-competitors,
expand by killing other cells. Novel cytotoxic drugs and molecularly targeted
drugs are commonly administered as part of cancer therapy. Both types of drugs
are susceptible to various mechanisms of drug resistance, obstructing or
preventing a successful outcome. In this paper, we develop a cancer growth
model that accounts for the competition between cancer cells and healthy cells.
The model incorporates resistance to both cytotoxic and targeted drugs. In both
cases, the level of drug resistance is assumed to be a continuous variable
ranging from fully-sensitive to fully-resistant. Using our model we demonstrate
that when the competition is moderate, therapies using both drugs are more
effective compared with single drug therapies. However, when cancer cells are
highly competitive, targeted drugs become more effective. In this case,
therapies that are initiated with a targeted drug and are exposed to it for a
sufficiently long time are shown to have better outcomes. The results of the
study stress the importance of adjusting the therapy to the pre-treatment
resistance levels. We conclude with a study of the spatiotemporal propagation
of drug resistance in a competitive setting, verifying that the same
conclusions hold in the spatially heterogeneous case.

Populations and Evolution;Tissues and Organs