Differential destruction of stem cells: implications for targeted cancer stem cell therapy.
Cancer stem cells represent a novel therapeutic target. The major challenge in targeting leukemic stem cells (LSC) is finding therapies that largely spare normal hematopoietic stem cells (HSC) while eradicating quiescent LSCs. We present a mathematical model to predict how selective a therapy must be to ensure that enough HSCs survive when LSCs have been eradicated. Stem cell population size is modeled as a birth-death process. This permits comparison of LSC and HSC eradication times under therapy and calculation of the number of HSCs at the time of LSC eradication for varied initial population sizes and stem cell death rates. We further investigate the effects of LSC quiescence and resistance mutations on our predictions. From a clinical point of view, our models suggest criteria by which cancer stem cell therapy safety can be assessed. We anticipate that in conjunction with experimental observation of cancer stem cell killing rates, our results will be useful in screening targeted therapies for both hematologic and solid tumor malignancies.
Sehl
Mary E
ME
Division of Hematology-Oncology, Department of Medicine, University of California, Los Angeles, California 90095-7059, USA. msehl@mednet.ucla.edu
Sinsheimer
Janet S
JS
Zhou
Hua
H
Lange
Kenneth L
KL
D000465:Algorithms; D003198:Computer Simulation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D007938:Leukemia / Q000473:pathology* / Q000628:therapy*; D008954:Models, Biological; D014411:Neoplastic Stem Cells / Q000473:pathology*; D013269:Stochastic Processes