Modeling early tumor development dynamics - implications for treatment design
by
Heiko Enderling
Center of Cancer Systems Biology, Caritas St. Elizabeth's Medical Center, Tufts University School of Medicine
Coauthors: Afshin Beheshti, Lynn Hlatky, Philip Hahnfeldt

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 for 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 through adjustments in other parameters that reduce the local density of progeny cells. The latter observation lends support to the theory that tumors grow in part through the creation and merging of local metastases. From the presented model we derive implications for treatment.

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Date received: May 13, 2008