Farnesyltransferase inhibition overcomes the adaptive resistance to osimertinib in EGFR-mutant NSCLC

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Figarol, Sarah | Delahaye, Célia | Gence, Rémi | Asslan, Raghda | Pagano, Sandra | Tardy, Claudine | Colinge, Jacques | Villemin, Jean-Philippe | Maraver, Antonio | Ferrer, Irene | Paz-Ares, Luis | Lajoie-Mazenc, Isabelle | Clermont, Estelle | Casanova, Anne | Pradines, Anne | Mazières, Julien | Calvayrac, Olivier | Favre, Gilles

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Drug-tolerant "dormant" cells (DTC) have emerged as one of the major non-genetic mechanisms driving resistance to targeted therapy in lung cancer, although the sequence of events leading to entry and exit from dormancy remain poorly described. Here, we performed real-time monitoring of the cell cycle dynamics during the adaptive response to Epidermal Growth Factor Receptor tyrosine kinase inhibitors (EGFR-TKi) in a panel of EGFR-mutated lung cancer cell lines. We identified a rare population of S/G2 cycling cells (referred to as early escapers) that emerged in the first

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