{"doi":"10.1101/2021.10.23.465573","title":"A focal adhesion kinase-YAP signaling axis drives drug tolerant persister cells and residual disease in lung cancer","abstract":"Abstract Targeted therapy is effective in many tumor types including lung cancer, the leading cause of cancer mortality. Paradigm defining examples are targeted therapies directed against non-small cell lung cancer (NSCLC) subtypes with oncogenic alterations in EGFR, ALK and KRAS. The success of targeted therapy is limited by drug-tolerant tumor cells which withstand and adapt to treatment and comprise the residual disease state that is typical during treatment with clinical targeted therapies. Here, we integrate studies in patient-derived and immunocompetent lung cancer models and clinical specimens obtained from patients on targeted therapy to uncover a focal adhesion kinase (FAK)-YAP signaling axis that promotes residual disease during oncogenic EGFR-, ALK-, and KRAS-targeted therapies. FAK-YAP signaling inhibition combined with the primary targeted therapy suppressed residual drug-tolerant cells and enhanced tumor responses. This study unveils a FAK-YAP signaling module that promotes residual disease in lung cancer and mechanism-based therapeutic strategies to improve tumor response.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":213611,"datarank":0.44166584687496613,"base_score":2.9444389791664403,"endowment":2.9444389791664403,"self_citation_contribution":0.44166584687496613,"citation_network_contribution":0.0,"self_endowment_contribution":0.44166584687496613,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9549,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":805666,"name":"Celia Fernández-Méndez","orcid":"0000-0001-8593-5507","position":1,"is_corresponding":false},{"id":249869,"name":"Lauren Čech","orcid":"0000-0002-3621-4129","position":2,"is_corresponding":false},{"id":315082,"name":"Johnny Yu","orcid":"0000-0002-9857-4349","position":3,"is_corresponding":false},{"id":634913,"name":"Ismail M. 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