{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T14:36:28Z","timestamp":1774535788950,"version":"3.50.1"},"reference-count":102,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,11,28]],"date-time":"2021-11-28T00:00:00Z","timestamp":1638057600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>ROS proto-oncogene 1 (ROS1) rearrangements are reported in about 1\u20132% of non-squamous non-small-cell lung cancer (NSCLC). After efficacy of crizotinib was demonstrated, identification of ROS1 translocations in advanced disease became fundamental to give patients the chance of specific and effective treatment. Different methods are available for detection of rearrangements, and probably the real prevalence of ROS1 rearrangements is higher than that reported in literature, as our capacity to detect gene rearrangements is improving. In particular, with next generation sequencing (NGS) techniques, we are currently able to assess multiple genes simultaneously with increasing sensitivity. This is leading to overcome the \u201csingle oncogenic driver\u201d paradigm, and in the very near future, the co-existence of multiple drivers will probably emerge more frequently and represent a therapeutic issue. Since recently, crizotinib has been the only available therapy, but today, many other tyrosine kinase inhibitors (TKI) are emerging and seem promising both in first and subsequent lines of treatment. Indeed, novel inhibitors are also able to overcome resistance mutations to crizotinib, hypothesizing a possible sequential strategy also in ROS1-rearranged disease. In this review, we will focus on ROS1 rearrangements, dealing with diagnostic aspects, new therapeutic options, resistance issues and the coexistence of ROS1 translocations with other molecular alterations.<\/jats:p>","DOI":"10.3390\/ijms222312867","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T23:22:28Z","timestamp":1638314548000},"page":"12867","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Deepening the Knowledge of ROS1 Rearrangements in Non-Small Cell Lung Cancer: Diagnosis, Treatment, Resistance and Concomitant Alterations"],"prefix":"10.3390","volume":"22","author":[{"given":"Giorgia","family":"Guaitoli","sequence":"first","affiliation":[{"name":"Ph.D. Program Clinical and Experimental Medicine (CEM), Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"},{"name":"Oncology and Hematology, Modena University Hospital, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Bertolini","sequence":"additional","affiliation":[{"name":"Oncology and Hematology, Modena University Hospital, 41125 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Bettelli","sequence":"additional","affiliation":[{"name":"Molecular Pathology, Modena University Hospital, 41125 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha","family":"Manfredini","sequence":"additional","affiliation":[{"name":"Molecular Pathology, Modena University Hospital, 41125 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michela","family":"Maur","sequence":"additional","affiliation":[{"name":"Oncology and Hematology, Modena University Hospital, 41125 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1260-2941","authenticated-orcid":false,"given":"Lucia","family":"Trudu","sequence":"additional","affiliation":[{"name":"Oncology and Hematology, Modena University Hospital, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5326-710X","authenticated-orcid":false,"given":"Beatrice","family":"Aramini","sequence":"additional","affiliation":[{"name":"Thoracic Surgery Unit, Department of Diagnostic and Specialty Medicine\u2014DIMES of the Alma Mater Studiorum, University of Bologna, G.B. 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