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Optimal pathways control fixation of multiple mutations during cancer initiation

Hamid Teimouri, Cade Spaulding, Anatoly B. Kolomeisky
doi: https://doi.org/10.1101/2022.02.07.479413
Hamid Teimouri
1Department of Chemistry, Rice University, Houston, Texas, United States
2Center for Theoretical Biological Physics, Rice University, Houston, Texas, United States
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Cade Spaulding
1Department of Chemistry, Rice University, Houston, Texas, United States
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Anatoly B. Kolomeisky
1Department of Chemistry, Rice University, Houston, Texas, United States
2Center for Theoretical Biological Physics, Rice University, Houston, Texas, United States
3Department of Chemical and Biomolecular Engineering, Rice University, Houston, Texas, United States
4Department of Physics and Astronomy, Rice University, Houston, TX, United States
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  • For correspondence: tolya@rice.edu
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Abstract

Cancer starts after initially healthy tissue cells accumulate several specific mutations or other genetic alterations. The dynamics of tumor formation is a very complex phenomenon due to multiple involved biochemical and biophysical processes. It leads to a very large number of possible pathways on the road to final fixation of all mutations that marks the beginning of the cancer, complicating the understanding of microscopic mechanisms of tumor formation. We present a new theoretical framework of analyzing the cancer initiation dynamics by exploring the properties of effective free-energy landscape of the process. It is argued that although there are many possible pathways for the fixation of all mutations in the system, there are only few dominating pathways on the road to tumor formation. The theoretical approach is explicitly tested in the system with only two mutations using analytical calculations and Monte Carlo computer simulations. Excellent agreement with theoretical predictions is found for a large range of parameters, supporting our hypothesis and allowing us to better understand the mechanisms of cancer initiation. Our theoretical approach clarifies some important aspects of microscopic processes that lead to tumor formation.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted February 09, 2022.
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Optimal pathways control fixation of multiple mutations during cancer initiation
Hamid Teimouri, Cade Spaulding, Anatoly B. Kolomeisky
bioRxiv 2022.02.07.479413; doi: https://doi.org/10.1101/2022.02.07.479413
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Optimal pathways control fixation of multiple mutations during cancer initiation
Hamid Teimouri, Cade Spaulding, Anatoly B. Kolomeisky
bioRxiv 2022.02.07.479413; doi: https://doi.org/10.1101/2022.02.07.479413

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