TY - JOUR
T1 - Modeling colorectal cancer evolution
AU - Niida, Atsushi
AU - Mimori, Koshi
AU - Shibata, Tatsuhiro
AU - Miyano, Satoru
N1 - Funding Information:
Acknowledgements We thank Dr. Takeshi Yamada for helpful discussion. This project was supported by JSPS Grant-in-Aid for Scientific Research on Innovative Areas (15H05912, 20H05039) and MEXT Fugaku Project (hp200138, hp210167).
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/9
Y1 - 2021/9
N2 - Understanding cancer evolution provides a clue to tackle therapeutic difficulties in colorectal cancer. In this review, together with related works, we will introduce a series of our studies, in which we constructed an evolutionary model of colorectal cancer by combining genomic analysis and mathematical modeling. In our model, multiple subclones were generated by driver mutation acquisition and subsequent clonal expansion in early-stage tumors. Among the subclones, the one obtaining driver copy number alterations is endowed with malignant potentials to constitute a late-stage tumor in which extensive intratumor heterogeneity is generated by the accumulation of neutral mutations. We will also discuss how to translate our understanding of cancer evolution to a solution to the problem related to therapeutic resistance: mathematical modeling suggests that relapse caused by acquired resistance could be suppressed by utilizing clonal competition between sensitive and resistant clones. Considering the current rate of technological development, modeling cancer evolution by combining genomic analysis and mathematical modeling will be an increasingly important approach for understanding and overcoming cancer.
AB - Understanding cancer evolution provides a clue to tackle therapeutic difficulties in colorectal cancer. In this review, together with related works, we will introduce a series of our studies, in which we constructed an evolutionary model of colorectal cancer by combining genomic analysis and mathematical modeling. In our model, multiple subclones were generated by driver mutation acquisition and subsequent clonal expansion in early-stage tumors. Among the subclones, the one obtaining driver copy number alterations is endowed with malignant potentials to constitute a late-stage tumor in which extensive intratumor heterogeneity is generated by the accumulation of neutral mutations. We will also discuss how to translate our understanding of cancer evolution to a solution to the problem related to therapeutic resistance: mathematical modeling suggests that relapse caused by acquired resistance could be suppressed by utilizing clonal competition between sensitive and resistant clones. Considering the current rate of technological development, modeling cancer evolution by combining genomic analysis and mathematical modeling will be an increasingly important approach for understanding and overcoming cancer.
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U2 - 10.1038/s10038-021-00930-0
DO - 10.1038/s10038-021-00930-0
M3 - Review article
C2 - 33986478
AN - SCOPUS:85105801489
VL - 66
SP - 869
EP - 878
JO - Jinrui idengaku zasshi. The Japanese journal of human genetics
JF - Jinrui idengaku zasshi. The Japanese journal of human genetics
SN - 1434-5161
IS - 9
ER -