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Mechanistically, EGFR TKIs increase the cytosolic level of calcium and trigger activation of a calcineurin\/MEK\/ERK pathway that prevents apoptosis. Combining EGFR, calcineurin, and MEK inhibitors overcomes resistance to EGFR TKI in both in vitro and in vivo models. Our results identify PPP3CB overexpression as a new mechanism of acquired resistance to EGFR TKIs, and provide a promising therapeutic approach for NSCLC patients that progress under TKI treatment.<\/jats:p>","DOI":"10.26508\/lsa.202402873","type":"journal-article","created":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T17:50:22Z","timestamp":1727805022000},"page":"e202402873","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["PPP3CB overexpression mediates EGFR TKI resistance in lung tumors via calcineurin\/MEK\/ERK signaling"],"prefix":"10.26508","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5817-1839","authenticated-orcid":true,"given":"Sylvie","family":"Gazzeri","sequence":"first","affiliation":[{"name":"University Grenoble Alpes, Inserm U1209, CNRS UMR 5309, Team RNA Splicing, Cell Signaling and Response to Therapy, Institute for Advanced Biosciences, Grenoble, 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