期刊
SYSTEMATIC BIOLOGY
卷 69, 期 4, 页码 623-637出版社
OXFORD UNIV PRESS
DOI: 10.1093/sysbio/syz070
关键词
Cancer; evolution; phylogenetics
资金
- University of Sheffield
- NIH Loan Repayment Program
- Paul Calabresi Career Development Award for Clinical Oncology [NIH K12CA076917]
- Cancer Systems Biology Consortium at the National Cancer Institute [U01CA232382, U54CA193489]
- Physical Sciences Oncology Network at the National Cancer Institute [U01CA232382, U54CA193489]
- Moffitt Center of Excellence for Evolutionary Therapy
We use a computational modeling approach to explore whether it is possible to infer a solid tumor's cellular proliferative hierarchy under the assumptions of the cancer stem cell hypothesis and neutral evolution. We work towards inferring the symmetric division probability for cancer stem cells, since this is believed to be a key driver of progression and therapeutic response. Motivated by the advent of multiregion sampling and resulting opportunities to infer tumor evolutionary history, we focus on a suite of statistical measures of the phylogenetic trees resulting from the tumor's evolution in different regions of parameter space and through time. We find strikingly different patterns in these measures for changing symmetric division probability which hinge on the inclusion of spatial constraints. These results give us a starting point to begin stratifying tumors by this biological parameter and also generate a number of actionable clinical and biological hypotheses regarding changes during therapy, and through tumor evolutionary time.
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