Acquired ROS1 Intragenic Rearrangements as a Resistance Mechanism in EGFR -Mutant Non-Small Cell Lung Cancer: A Case Series.
Simple Summary: We describe three women with EGFR-mutant lung cancer in whom a rare ROS1 exon 35–37 RNA-level intragenic rearrangement was detected after progression on EGFR-targeted therapy. Our series demonstrates that combining two different targeted therapies to block both mutations can lead to...
| Publicado en: | Current Oncology Vol. 33; no. 6; pp. 311 - 323 |
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| Autores principales: | , , , , |
| Formato: | Journal Article |
| Publicado: |
MDPI
Jun2026
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=194912087&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 194912087 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 11980052 5EKK jtl: Current Oncology issn: 11980052 maglogo: N pubinfo: dt: Jun2026 vid: 33 iid: 6 pid: 97109 pub: MDPI artinfo: ui: 194912087 10.3390/curroncol33060311 194912087 ppf: 311 ppct: 12 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Acquired ROS1 Intragenic Rearrangements as a Resistance Mechanism in EGFR -Mutant Non-Small Cell Lung Cancer: A Case Series. aug: au: Liu, Po-Tsen Chen, Yi-Lin Chen, Wan-Li Ho, Chung-Liang Lee, Chun-Hui affil: Division of Hematology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan sug: ab: Simple Summary: We describe three women with EGFR-mutant lung cancer in whom a rare ROS1 exon 35–37 RNA-level intragenic rearrangement was detected after progression on EGFR-targeted therapy. Our series demonstrates that combining two different targeted therapies to block both mutations can lead to long-term survival in one case, but another case may experience significant side effects. When combined therapy is not tolerated, traditional chemotherapy remains a necessary and effective alternative. This study highlights the potential value of advanced molecular testing after treatment failure and underscores the need for individualized treatment strategies and further functional validation when this specific ROS1 rearrangement is detected. Lung cancer is a leading cause of global cancer mortality, with EGFR mutations serving as a primary therapeutic target. Although EGFR tyrosine kinase inhibitors (TKIs) are initially effective, acquired resistance inevitably develops. While ROS1 rearrangements are well-known baseline drivers, they are exceptionally rare as acquired resistance mechanisms. We utilized next-generation sequencing (NGS) to identify a rare ROS1 intragenic rearrangement (exons 35–37) in three never-smoking women with EGFR-mutant lung adenocarcinoma following progression on EGFR TKIs. Clinical courses were heterogeneous: one patient achieved a durable partial response using combined osimertinib and crizotinib. A second patient, intolerant to dual TKI therapy due to QTc prolongation and grade 3 edemas, achieved a sustained partial response with platinum-pemetrexed chemotherapy. The third patient exhibited polyclonal resistance, including EGFR C797S and TP53 mutations, with fatal central nervous system progression. In this three-patient case series, ROS1 exon 35–37 RNA-level intragenic rearrangements were repeatedly detected after EGFR-TKI progression, suggesting a rare transcript-level alteration within heterogeneous resistance evolution. However, its biological significance, driver versus passenger role, and therapeutic relevance remain uncertain. Combined EGFR and ROS1 inhibition may be considered in selected cases, but further validation is required. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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