Drug-induced colorectal cancer persister cells show increased mutation rate

Russo, M.; Pompei, S.; Sogari, A.; Corigliano, M.; Crisafulli, G.; Bertotti, A.; Gherardi, M.; Di Nicolantonio, F.; Bardelli, A.; Lagomarsino, M. C.

doi:10.1101/2021.05.17.444478

bioRxiv · 10.1101/2021.05.17.444478

Drug-induced colorectal cancer persister cells show increased mutation rate

Russo, M.·Pompei, S.·Sogari, A.·Corigliano, M.·Crisafulli, G.·Bertotti, A.·Gherardi, M.·Di Nicolantonio, F.·Bardelli, A.·Lagomarsino, M. C.

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Abstract

Compelling evidence shows that cancer persister cells limit the efficacy of targeted therapies. However, it is unclear whether persister cells are induced by anticancer drugs, and if their mutation rate quantitatively increases during treatment. Here, combining experimental characterization and mathematical modeling, we show that, in colorectal cancer, persisters are induced by drug treatment and show a 7- to 50-fold increase of mutation rate when exposed to clinically approved targeted therapies. These findings reveal that treatment may influence persistence and mutability in cancer cells and pinpoints new strategies to restrict tumor recurrence.

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Russo, M., Pompei, S., Sogari, A., Corigliano, M., Crisafulli, G., Bertotti, A., Gherardi, M., Di Nicolantonio, F., Bardelli, A., Lagomarsino, M. C.. 2021-05-17. Drug-induced colorectal cancer persister cells show increased mutation rate. https://doi.org/10.1101/2021.05.17.444478

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