Adaptive mutability of colorectal cancers in response to targeted therapies

Russo, Mariangela; Crisafulli, Giovanni; Sogari, Alberto; Reilly, Nicole M.; Arena, Sabrina; Lamba, Simona; Bartolini, Alice; Amodio, Vito; Magrì, Alessandro; Novara, Luca; Sarotto, Ivana; Nagel, Zachary D.; Piett, Cortt G.; Amatu, Alessio; Sartore‐Bianchi, Andrea; Siena, Salvatore; Bertotti, Andrea; Trusolino, Livio; Corigliano, Mattia; Gherardi, Marco; Lagomarsino, Marco Cosentino; Nicolantonio, Federica Di; Bardelli, Alberto

doi:10.1126/science.aav4474

articleScienceNov 7, 2019GREEN OA

Adaptive mutability of colorectal cancers in response to targeted therapies

MRMariangela Russo GCGiovanni Crisafulli ASAlberto Sogari NMNicole M. Reilly SASabrina Arena

Candiolo Cancer Institute · Fondazione Piemontese per la Ricerca sul Cancro Onlus · +4 more institutions

PubMed

Indexed incrossrefpubmed

Abstract

The emergence of drug resistance limits the efficacy of targeted therapies in human tumors. The prevalent view is that resistance is a fait accompli: when treatment is initiated, cancers already contain drug-resistant mutant cells. Bacteria exposed to antibiotics transiently increase their mutation rates (adaptive mutability), thus improving the likelihood of survival. We investigated whether human colorectal cancer (CRC) cells likewise exploit adaptive mutability to evade therapeutic pressure. We found that epidermal growth factor receptor (EGFR)/BRAF inhibition down-regulates mismatch repair (MMR) and homologous recombination DNA-repair genes and concomitantly up-regulates error-prone polymerases in…

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445

total citations

FWCI: 17.07
Percentile: 100%
References: 62

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Authors

23

Topics & keywords

Topics

Keywords

Microsatellite instability
Homologous recombination
Colorectal cancer
DNA mismatch repair
Cancer research
Biology
DNA repair
Mutation

UN Sustainable Development Goals

Good health and well-being

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