Modeling age-specific incidence of colon cancer via niche competition Artikel uri icon

Open Access

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Peer Reviewed

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Abstract

  • PLoS Comput Biol 18(8): e1010403 (2022) 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.

Veröffentlichungszeitpunkt

  • August 1, 2022