AXL and Error-Prone DNA Replication Confer Drug Resistance and Offer Strategies to Treat EGFR-Mutant Lung Cancer.

Ashish Noronha Nishanth Belugali Nataraj Joo Sang Lee Benny Zhitomirsky Yaara Oren Sara Oster Moshit Lindzen Saptaparna Mukherjee Rainer WillSoma GhoshArturo Simoni-Nieves Aakanksha Verma Rishita Chatterjee Simone Borgoni Welles Robinson Sanju Sinha Alexander Brandis D Lucas Kerr Wei Wu Arunachalam Sekar Suvendu Giri Youngmin Chung Diana Drago-Garcia Brian P Danysh Mattia Lauriola Michelangelo Fiorentino Andrea Ardizzoni Moshe Oren Collin M Blakely Jideofor Ezike Stefan Wiemann Laxmi Parida Trever G Bivona Rami I Aqeilan Joan S Brugge Aviv Regev Gad A Getz Eytan Ruppin Yosef Yarden

Published in: Cancer discovery (2022)

EGFR-mutant lung cancers treated with kinase inhibitors often evolve resistance due to secondary mutations. We report that in similarity to the bacterial SOS response stimulated by antibiotics, endogenous mutators are activated in drug-treated cells, and this heralds tolerance. Blocking the process prevented resistance in xenograft models, which offers new treatment strategies. This article is highlighted in the In This Issue feature, p. 2483.

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