Open AccessCrypt dynamics and colorectal cancer: advances in mathematical modelling
Author(s) -
Van Leeuwen I. M. M.,
Byrne H. M.,
Jensen O. E.,
King J. R.
Publication year - 2006
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/j.1365-2184.2006.00378.x
Subject(s) - crypt , stem cell , biology , colorectal cancer , computational biology , aberrant crypt foci , evolutionary dynamics , carcinogenesis , cell division , cell , microbiology and biotechnology , cancer , genetics , medicine , population , colonic disease , environmental health , endocrinology
Abstract. Mathematical modelling forms a key component of systems biology, offering insights that complement and stimulate experimental studies. In this review, we illustrate the role of theoretical models in elucidating the mechanisms involved in normal intestinal crypt dynamics and colorectal cancer. We discuss a range of modelling approaches, including models that describe cell proliferation, migration, differentiation, crypt fission, genetic instability, APC inactivation and tumour heterogeneity. We focus on the model assumptions, limitations and applications, rather than on the technical details. We also present a new stochastic model for stem‐cell dynamics, which predicts that, on average, APC inactivation occurs more quickly in the stem‐cell pool in the absence of symmetric cell division. This suggests that natural niche succession may protect stem cells against malignant transformation in the gut. Finally, we explain how we aim to gain further understanding of the crypt system and of colorectal carcinogenesis with the aid of multiscale models that cover all levels of organization from the molecular to the whole organ.