1 research outputs found
Modeling age-specific incidence of colon cancer via niche competition
Cancer development is a multistep process often starting with a single cell
in which a number of epigenetic and genetic alterations have accumulated thus
transforming it into a tumor cell. The progeny of such a single benign tumor
cell expands in the tissue and can at some point progress to malignant tumor
cells until a detectable tumor is formed. The dynamics from the early phase of
a single cell to a detectable tumor with billions of tumor cells are complex
and still not fully resolved, not even for the well-known prototype of
multistage carcinogenesis, the adenoma-adenocarcinoma sequence of colorectal
cancer. Mathematical models of such carcinogenesis are frequently tested and
calibrated based on reported age-specific incidence rates of cancer, but they
usually require calibration of four or more parameters due to the wide range of
processes these models aim to reflect. We present a cell-based model, which
focuses on the competition between wild-type and tumor cells in colonic crypts,
with which we are able reproduce epidemiological incidence rates of colon
cancer. Additionally, the fraction of cancerous tumors with precancerous
lesions predicted by the model agree with clinical estimates. The
correspondence between model and reported data suggests that the fate of tumor
development is majorly determined by the early phase of tumor growth and
progression long before a tumor becomes detectable. Due to the focus on the
early phase of tumor development, the model has only a single fit parameter,
the time scale set by an effective replacement rate of stem cells in the crypt.
We find this effective rate to be considerable smaller than the actual
replacement rate, which implies that the time scale is limited by the processes
succeeding clonal conversion of crypts.Comment: 28 pages, 13 figure