Version 1
: Received: 1 July 2022 / Approved: 4 July 2022 / Online: 4 July 2022 (04:56:00 CEST)
How to cite:
Jain, P.; Duddu, A.S.; Jolly, M.K. Stochastic Population Dynamics of Cancer Stemness and Adaptive Response to Therapies. Preprints2022, 2022070031. https://doi.org/10.20944/preprints202207.0031.v1
Jain, P.; Duddu, A.S.; Jolly, M.K. Stochastic Population Dynamics of Cancer Stemness and Adaptive Response to Therapies. Preprints 2022, 2022070031. https://doi.org/10.20944/preprints202207.0031.v1
Jain, P.; Duddu, A.S.; Jolly, M.K. Stochastic Population Dynamics of Cancer Stemness and Adaptive Response to Therapies. Preprints2022, 2022070031. https://doi.org/10.20944/preprints202207.0031.v1
APA Style
Jain, P., Duddu, A.S., & Jolly, M.K. (2022). Stochastic Population Dynamics of Cancer Stemness and Adaptive Response to Therapies. Preprints. https://doi.org/10.20944/preprints202207.0031.v1
Chicago/Turabian Style
Jain, P., Atchuta Srinivas Duddu and Mohit Kumar Jolly. 2022 "Stochastic Population Dynamics of Cancer Stemness and Adaptive Response to Therapies" Preprints. https://doi.org/10.20944/preprints202207.0031.v1
Abstract
Intratumoral heterogeneity can exist along multiple axes: Cancer Stem Cells (CSCs)/non-CSCs, drug-sensitive/drug-tolerant states and a spectrum of epithelial-hybrid-mesenchymal phenotypes. Further, these diverse cell-states can switch reversibly among one another, thereby posing a major challenge to therapeutic efficacy. Therefore, understanding the origins of phenotypic plasticity and heterogeneity remains an active area of investigation. While genomic components (mutations, chromosomal instability) driving heterogeneity have been well-studied, recent reports highlight the role of non-genetic mechanisms in enabling both phenotypic plasticity and heterogeneity. Here, we discuss various processes underlying phenotypic plasticity such as stochastic gene expression, chromatin reprogramming, asymmetric cell division and the presence of multiple “attractors”. These processes can facilitate a dynamically evolving cell population such that a subpopulation of (drug-tolerant) cells can survive lethal drug exposure and recapitulate population heterogeneity on drug withdrawal, leading to relapse. These drug-tolerant cells can be both pre-existing and also induced by the drug itself through cell-state reprogramming. The dynamics of cell-state transitions both in absence and presence of the drug can be quantified through mathematical models. Such a dynamical systems approach to elucidating patterns of intratumoral heterogeneity by integrating longitudinal experimental data with mathematical models can help design effective combinatorial and/or sequential therapies for better clinical outcomes.
Keywords
Cell-state transitions; Phenotypic plasticity; Cancer Stem Cells; Intratumoral heterogeneity; Lamarckian Induction; Drug resistance
Subject
Biology and Life Sciences, Biophysics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
