{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nROS1 is a receptor tyrosine kinase whose gene rearrangements result in novel fusion proteins that retain its kinase domain and become constitutively active. Such aberrant activation drives oncogenic signaling by promoting uncontrolled cell proliferation, survival, and invasive potential. This mechanism has been identified in various cancers – most notably in non–small-cell lung cancer (NSCLC), but also in cholangiocarcinoma, inflammatory myofibroblastic tumors, and several other malignancies – thereby establishing ROS1 fusions as key oncogenic drivers with strong dependency on downstream signaling pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "13"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDiagnostic studies have leveraged immunohistochemistry, fluorescence in situ hybridization, and reverse transcription–PCR to reliably detect ROS1 rearrangements. Histopathologically, ROS1 fusion–positive tumors exhibit distinct morphologies and clinical features, including a tendency to occur in younger or never‐smoking patients. Importantly, the constitutive kinase activity renders these tumors exquisitely sensitive to ROS1 inhibitors (for example, crizotinib), although a subset eventually acquires resistance through secondary mutations (such as the G2032R change) or alterations in signaling dependencies. Moreover, variability among fusion partners can influence subcellular localization and downstream pathway activation (for instance, differential engagement of MAPK cascades), thereby modulating tumor aggressiveness."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "26"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTherapeutically, the identification of ROS1 fusions has led to significant advances by enabling the use of targeted inhibitors that produce robust clinical responses. Clinical trials and subsequent FDA approvals underscore the benefit of early targeted therapy; yet, acquired resistance remains a challenge due to secondary kinase domain mutations and shifts in oncogenic signaling networks (for example, compensatory activation of EGFR pathways). Ongoing genomic and preclinical studies continue to refine our understanding of how fusion breakpoint variability and partner selection can influence both the biological behavior of ROS1 fusion proteins and the efficacy of targeted inhibitors, thereby guiding the development of next‐generation agents to overcome resistance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "27", "end_ref": "40"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ting-Lei Gu, Xiaxing Deng, Feizhou Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Survey of tyrosine kinase signaling reveals ROS kinase fusions in human cholangiocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0015640"}], "href": "https://doi.org/10.1371/journal.pone.0015640"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21253578"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21253578"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kristin Bergethon, Alice T Shaw, Sai-Hong Ignatius Ou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ROS1 rearrangements define a unique molecular class of lung cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Oncol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1200/JCO.2011.35.6345"}], "href": "https://doi.org/10.1200/JCO.2011.35.6345"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22215748"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22215748"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kengo Takeuchi, Manabu Soda, Yuki Togashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RET, ROS1 and ALK fusions in lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm.2658"}], "href": "https://doi.org/10.1038/nm.2658"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22327623"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22327623"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Hiroyuki Yasuda, Lorena L de Figueiredo-Pontes, Susumu Kobayashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Preclinical rationale for use of the clinically available multitargeted tyrosine kinase inhibitor crizotinib in ROS1-translocated lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thorac Oncol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/JTO.0b013e3182570919"}], "href": "https://doi.org/10.1097/JTO.0b013e3182570919"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22617245"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22617245"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Victoria M Rimkunas, Katherine E Crosby, Daiqiang Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of receptor tyrosine kinase ROS1-positive tumors in non-small cell lung cancer: identification of a FIG-ROS1 fusion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-11-3351"}], "href": "https://doi.org/10.1158/1078-0432.CCR-11-3351"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22661537"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22661537"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Hyun Jung Jun, Hannah Johnson, Roderick T Bronson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The oncogenic lung cancer fusion kinase CD74-ROS activates a novel invasiveness pathway through E-Syt1 phosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-11-3990"}], "href": "https://doi.org/10.1158/0008-5472.CAN-11-3990"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22659450"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22659450"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jeeyun Lee, Seung Eun Lee, So Young Kang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of ROS1 rearrangement in gastric adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cncr.27967"}], "href": "https://doi.org/10.1002/cncr.27967"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23400546"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23400546"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Geoffrey R Oxnard, Adam Binder, Pasi A Jänne "}, {"type": "b", "children": [{"type": "t", "text": "New targetable oncogenes in non-small-cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Oncol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1200/JCO.2012.42.9829"}], "href": "https://doi.org/10.1200/JCO.2012.42.9829"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23401445"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23401445"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Akihiko Yoshida, Takashi Kohno, Koji Tsuta, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ROS1-rearranged lung cancer: a clinicopathologic and molecular study of 15 surgical cases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Surg Pathol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/PAS.0b013e3182758fe6"}], "href": "https://doi.org/10.1097/PAS.0b013e3182758fe6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23426121"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23426121"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "W Cai, X Li, C Su, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ROS1 fusions in Chinese patients with non-small-cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Oncol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/annonc/mdt071"}], "href": "https://doi.org/10.1093/annonc/mdt071"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23514723"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23514723"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Kurtis D Davies, Robert C Doebele "}, {"type": "b", "children": [{"type": "t", "text": "Molecular pathways: ROS1 fusion proteins in cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-12-2851"}], "href": "https://doi.org/10.1158/1078-0432.CCR-12-2851"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23719267"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23719267"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "H R Kim, S M Lim, H J Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The frequency and impact of ROS1 rearrangement on clinical outcomes in never smokers with lung adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Oncol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/annonc/mdt220"}], "href": "https://doi.org/10.1093/annonc/mdt220"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23788756"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23788756"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Lynette M Sholl, Heather Sun, Mohit Butaney, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ROS1 immunohistochemistry for detection of ROS1-rearranged lung adenocarcinomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Surg Pathol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/PAS.0b013e3182960fa7"}], "href": "https://doi.org/10.1097/PAS.0b013e3182960fa7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23887156"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23887156"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Kurtis D Davies, Sakshi Mahale, David P Astling, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Resistance to ROS1 inhibition mediated by EGFR pathway activation in non-small cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0082236"}], "href": "https://doi.org/10.1371/journal.pone.0082236"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24349229"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24349229"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Arne Warth, Thomas Muley, Hendrik Dienemann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ROS1 expression and translocations in non-small-cell lung cancer: clinicopathological analysis of 1478 cases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Histopathology (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/his.12379"}], "href": "https://doi.org/10.1111/his.12379"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24456475"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24456475"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Yunjian Pan, Yang Zhang, Yuan Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ALK, ROS1 and RET fusions in 1139 lung adenocarcinomas: a comprehensive study of common and fusion pattern-specific clinicopathologic, histologic and cytologic features."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lung Cancer (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.lungcan.2014.02.007"}], "href": "https://doi.org/10.1016/j.lungcan.2014.02.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24629636"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24629636"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Ryohei Katayama, Yuka Kobayashi, Luc Friboulet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cabozantinib overcomes crizotinib resistance in ROS1 fusion-positive cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-14-1385"}], "href": "https://doi.org/10.1158/1078-0432.CCR-14-1385"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25351743"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25351743"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Jason L Hornick, Lynette M Sholl, Paola Dal Cin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of ROS1 predicts ROS1 gene rearrangement in inflammatory myofibroblastic tumors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mod Pathol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/modpathol.2014.165"}], "href": "https://doi.org/10.1038/modpathol.2014.165"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25612511"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25612511"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Julien Mazières, Gérard Zalcman, Lucio Crinò, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Crizotinib therapy for advanced lung adenocarcinoma and a ROS1 rearrangement: results from the EUROS1 cohort."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Oncol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1200/JCO.2014.58.3302"}], "href": "https://doi.org/10.1200/JCO.2014.58.3302"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25667280"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25667280"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Ahnah Song, Tae Min Kim, Dong-Wan Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular Changes Associated with Acquired Resistance to Crizotinib in ROS1-Rearranged Non-Small Cell Lung Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-14-1350"}], "href": "https://doi.org/10.1158/1078-0432.CCR-14-1350"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25688157"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25688157"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Cristina R Antonescu, Albert J H Suurmeijer, Lei Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular characterization of inflammatory myofibroblastic tumors with frequent ALK and ROS1 gene fusions and rare novel RET rearrangement."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Surg Pathol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/PAS.0000000000000404"}], "href": "https://doi.org/10.1097/PAS.0000000000000404"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25723109"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25723109"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Toni-Maree Rogers, Prudence A Russell, Gavin Wright, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Comparison of methods in the detection of ALK and ROS1 rearrangements in lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thorac Oncol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/JTO.0000000000000465"}], "href": "https://doi.org/10.1097/JTO.0000000000000465"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25789833"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25789833"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "E Pailler, N Auger, C R Lindsay, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High level of chromosomal instability in circulating tumor cells of ROS1-rearranged non-small-cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Oncol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/annonc/mdv165"}], "href": "https://doi.org/10.1093/annonc/mdv165"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25846554"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25846554"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Matthias Scheffler, Anne Schultheis, Cristina Teixido, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ROS1 rearrangements in lung adenocarcinoma: prognostic impact, therapeutic options and genetic variability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.3387"}], "href": "https://doi.org/10.18632/oncotarget.3387"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25868855"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25868855"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Hidetaka Yamamoto, Akihiko Yoshida, Kenichi Taguchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ALK, ROS1 and NTRK3 gene rearrangements in inflammatory myofibroblastic tumours."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Histopathology (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/his.12910"}], "href": "https://doi.org/10.1111/his.12910"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26647767"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26647767"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Alexander Drilon, Romel Somwar, Jacob P Wagner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Novel Crizotinib-Resistant Solvent-Front Mutation Responsive to Cabozantinib Therapy in a Patient with ROS1-Rearranged Lung Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-15-2013"}], "href": "https://doi.org/10.1158/1078-0432.CCR-15-2013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26673800"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26673800"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Arnaud Uguen, Marc De Braekeleer "}, {"type": "b", "children": [{"type": "t", "text": "ROS1 fusions in cancer: a review."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Future Oncol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2217/fon-2016-0050"}], "href": "https://doi.org/10.2217/fon-2016-0050"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27256160"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27256160"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Dickran Kazandjian, Gideon M Blumenthal, Lola Luo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Benefit-Risk Summary of Crizotinib for the Treatment of Patients With ROS1 Alteration-Positive, Metastatic Non-Small Cell Lung Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncologist (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1634/theoncologist.2016-0101"}], "href": "https://doi.org/10.1634/theoncologist.2016-0101"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27328934"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27328934"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Francesco Facchinetti, Yohann Loriot, Mei-Shiue Kuo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Crizotinib-Resistant ROS1 Mutations Reveal a Predictive Kinase Inhibitor Sensitivity Model for ROS1- and ALK-Rearranged Lung Cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-16-0917"}], "href": "https://doi.org/10.1158/1078-0432.CCR-16-0917"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27401242"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27401242"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Marcel Wiesweg, Wilfried E E Eberhardt, Henning Reis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High Prevalence of Concomitant Oncogene Mutations in Prospectively Identified Patients with ROS1-Positive Metastatic Lung Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thorac Oncol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jtho.2016.08.137"}], "href": "https://doi.org/10.1016/j.jtho.2016.08.137"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27575422"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27575422"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Jessica J Lin, Lauren L Ritterhouse, Siraj M Ali, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ROS1 Fusions Rarely Overlap with Other Oncogenic Drivers in Non-Small Cell Lung Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thorac Oncol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jtho.2017.01.004"}], "href": "https://doi.org/10.1016/j.jtho.2017.01.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28088512"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28088512"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Filippo Pietrantonio, Federica Di Nicolantonio, Alexa B Schrock, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ALK, ROS1, and NTRK Rearrangements in Metastatic Colorectal Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Natl Cancer Inst (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/jnci/djx089"}], "href": "https://doi.org/10.1093/jnci/djx089"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29370427"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29370427"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Ziming Li, Lan Shen, Ding Ding, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Efficacy of Crizotinib among Different Types of ROS1 Fusion Partners in Patients with ROS1-Rearranged Non-Small Cell Lung Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thorac Oncol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jtho.2018.04.016"}], "href": "https://doi.org/10.1016/j.jtho.2018.04.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29704675"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29704675"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Sehhoon Park, Beung-Chul Ahn, Sung Won Lim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characteristics and Outcome of ROS1-Positive Non-Small Cell Lung Cancer Patients in Routine Clinical Practice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thorac Oncol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jtho.2018.05.026"}], "href": "https://doi.org/10.1016/j.jtho.2018.05.026"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29883837"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29883837"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Tejas Patil, Derek E Smith, Paul A Bunn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Incidence of Brain Metastases in Stage IV ROS1-Rearranged Non-Small Cell Lung Cancer and Rate of Central Nervous System Progression on Crizotinib."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thorac Oncol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jtho.2018.07.001"}], "href": "https://doi.org/10.1016/j.jtho.2018.07.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29981925"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29981925"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Dana S Neel, David V Allegakoen, Victor Olivas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential Subcellular Localization Regulates Oncogenic Signaling by ROS1 Kinase Fusion Proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-18-1492"}], "href": "https://doi.org/10.1158/0008-5472.CAN-18-1492"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30538120"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30538120"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Ryohei Katayama, Bo Gong, Noriko Togashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The new-generation selective ROS1/NTRK inhibitor DS-6051b overcomes crizotinib resistant ROS1-G2032R mutation in preclinical models."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-019-11496-z"}], "href": "https://doi.org/10.1038/s41467-019-11496-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31399568"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31399568"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Giuseppe Lamberti, Elisa Andrini, Monia Sisi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Beyond EGFR, ALK and ROS1: Current evidence and future perspectives on newly targetable oncogenic drivers in lung adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Crit Rev Oncol Hematol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.critrevonc.2020.103119"}], "href": "https://doi.org/10.1016/j.critrevonc.2020.103119"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33053439"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33053439"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Weihua Li, Lei Guo, Yutao Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Potential Unreliability of Uncommon ALK, ROS1, and RET Genomic Breakpoints in Predicting the Efficacy of Targeted Therapy in NSCLC."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thorac Oncol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jtho.2020.10.156"}], "href": "https://doi.org/10.1016/j.jtho.2020.10.156"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33248323"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33248323"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Jessica J Lin, Noura J Choudhury, Satoshi Yoda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Spectrum of Mechanisms of Resistance to Crizotinib and Lorlatinib in "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "ROS1"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " Fusion-Positive Lung Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-21-0032"}], "href": "https://doi.org/10.1158/1078-0432.CCR-21-0032"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33685866"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33685866"}]}]}]}