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Adaptation to inhibitors of ERK signaling

Cancer cells are wired to adapt to many targeted therapies currently used to treat cancer patients. By adaptation we refer to a process whereby initial inhibition of the target oncoprotein is bypassed shortly after drug treatment, as a consequence of alterations in signaling dynamics. This is particularly the case with inhibitors of the ERK signaling pathway (reviewed in Nature Medicine, 2013; PMID: 24202393). Indeed tumor cell adaptation limits the therapeutic response to RAF inhibitors in BRAF-mutant melanomas (Cancer Cell, 2012; PMID: 23153539), or that of MEK inhibitors in KRAS-mutant cancers (Cancer Cell, 2014; PMID: 24746704).

Current efforts aim to study this process in patient-derived lung cancer models and to determine if it contributes to the emergence of acquired resistance.