Evolutionary rescue by aneuploidy in tumors exposed to anti-cancer drugs

This is a Preprint and has not been peer reviewed. This is version 1 of this Preprint.

Add a Comment

You must log in to post a comment.


Comments

There are no comments or no comments have been made public for this article.

Downloads

Download Preprint

Authors

Remus Stana, Uri Ben-David, Daniel B Weissman, Yoav Ram

Abstract

Evolutionary rescue happens when a population survives a sudden environmental change that initially causes the population to decline toward extinction. A prime example of evolutionary rescue is the ability of cancer to survive exposure to treatment. One evolutionary mechanism by which a population of cancer cells can adapt to chemotherapy is aneuploidy. Aneuploid cancer cells can be fitter in an environment altered by anti-cancer drugs, e.g., because aneuploidy disrupts the pathways usually targeted by the drugs. Indeed, aneuploidy is highly prevalent in tumors, and some anti-cancer drugs fight cancer by increasing chromosomal instability. Here, we model the impact of aneuploidy on the fate of a population of cancer cells. We use multi-type branching processes to approximate the probability that a tumor survives drug treatment as a function of the initial tumor size, the rates at which aneuploidy and other beneficial mutations occur, and the growth rates of the drug-sensitive and drug-resistant cells. Additionally, we investigate the effect of the pre-existent aneuploid cells on the probability of evolutionary rescue. Finally, we estimate the tumor’s mean recurrence time to revert to its initial size following treatment and evolutionary rescue. We propose that aneuploidy can play an essential role in the relapse of smaller secondary tumors.

DOI

https://doi.org/10.32942/X26K8C

Subjects

Ecology and Evolutionary Biology, Evolution, Genetics, Life Sciences

Keywords

aneuploidy, evolutionary model, adaptive evolution, Cancer, drug resistance, chromosome instability

Dates

Published: 2024-07-31 14:22

License

CC-By Attribution-ShareAlike 4.0 International

Additional Metadata

Language:
English

Conflict of interest statement:
None

Data and Code Availability Statement:
Not applicable