An in-silico model of early tumor development dynamics - implications for treatment design
- Date: 03/10/2008
Heiko Enderling Tufts University School of Medicine, Boston
University of Alberta
Cancer development may be considered an evolutionary process whereby genetically unstable cell clones compete under selective influences of the local environment and succeed in accordance with the relative fitnesses of their expressed phenotypes. The competition process involves traversal through a number of bottleneck challenges at all phases of tumor development. One factor limiting tumor cell proliferation is space to grow, a condition which may be alleviated by cell death within the mass. We show theoretically how tumor populations devoid of stem cells could still persist as long-term dormant lesions, and offer a possible explanation of the incidence of dormant tumors observed in recent autopsy studies. This finding questions the notion that tumors escaping dormancy will necessarily become symptomatic. Finally, if the tumor population is assumed to contain cancer stem cells, we show 1) that certain conditions may paradoxically limit the growth of the lesion, even if it escapes dormancy, and 2) the number of stem cells can be amplified by shifting the parameters of different mechanisms. From the latter observation we lend support to the theory that tumors grow in part through the creation and merging of local metastases. From the presented model we will derive implications for treatment.
PIMS Mathematical Biology Seminar