  Tumours are made up of a mixed population of different types of cells that
include normal struc- tures as well as ones associated with the malignancy, and
there are multiple interactions between the malignant cells and the local
microenvironment. These intercellular interactions, modulated by the
microenvironment, effect tumour progression and represent a largely under
appreciated therapeutic target. We use observations of primary tumor biology
from prostate cancer to extrapolate a math- ematical model: specifically; it
has been observed that in prostate cancer three disparate cellular outcomes
predominate: (i) the tumour remains well differentiated and clinically indolent
- in this case the local stromal cells may act to restrain the growth of the
cancer; (ii) early in its genesis the tumour acquires a highly malignant
phenotype, growing rapidly and displacing the original stromal population
(often referred to as small cell prostate cancer) - these less common
aggressive tumours are relatively independent of the local microenvironment;
and, (iii) the tumour co-opts the local stroma - taking on a classic
stromagenic phenotype where interactions with the local microenviron- ment are
critical to the cancer growth. We present an evolutionary game theoretical
construct that models the influence of tumour-stroma interactions in driving
these outcomes. We consider three characteristic and distinct cellular
populations: stromal cells, tumour cells that are self-reliant in terms of
microenvironmental factors and tumour cells that depend on the environment for
resources but can also co-opt stroma. Using evolutionary game theory we explore
a number of different sce- narios that elucidate the impact of tumour-stromal
interactions on the dynamics of prostate cancer growth and progression and how
different treatments in the metastatic setting can affect different types of
tumors.
