ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

In conclusion, this work consolidates practical recommendations for integrating optimized gene fusion detection into routine clinical workflows. These include guidance on assay design, quality control measures, and method validation, to ensure the delivery of reliable results to support personalized treatment strategies in NSCLC.

Nearly 7% of EGFR mutations in NSCLC patients were compound mutations, which is comparable to previous reports. The presence of multiple mutations, particularly those involving T790M , may be associated with potential resistance to first-line EGFR -TKIs. We describe a triple mutation involving del19 + G719X + S768I , which represents an uncommon scenario.

P3, N=878, Recruiting, AstraZeneca | Trial completion date: Mar 2030 --> Nov 2030 | Trial primary completion date: May 2029 --> Nov 2030

P1/2, N=77, Suspended, University of California, Davis | Trial completion date: Jan 2030 --> Jan 2034 | Recruiting --> Suspended | Trial primary completion date: Jan 2026 --> Dec 2030

We aimed to evaluate and compare the efficacy and safety of atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) versus pemetrexed plus carboplatin or cisplatin (PC) in patients with progressive NSCLC harboring EGFR, ALK, or ROS1 alterations after TKI failure. ABCP significantly improved PFS compared with PC in patients with NSCLC that progressed despite prior TKI therapy. An OS benefit was observed in patients with three or more metastatic sites.

EGR1 and PTGS2 are central nodes through which APM precipitates MASLD and accelerates progression to HCC. We propose a "dual-track" oncogenic paradigm: Track A follows the canonical MASLD-HCC axis (bile-acid retention - lipid deposition - TNF/IL-17-driven ROS-mutational amplification), whereas Track B allows APM, via PTGS2/EGR1, to usurp gate-keeper proteins governing proliferation and apoptosis, initiating malignant programming before overt steatosis develops. These findings provide mechanistic insight into APM-related hepatocarcinogenesis, nominate tractable diagnostic biomarkers and therapeutic targets, and inform future re-evaluation of APM carcinogenicity classifications.

These findings highlight recurrent alterations in TP53, RB1, and ATRX and suggest potential roles for IGF2 and AXIN1 in leiomyosrcoma metastatic disease that warrant further investigation.

This multicentre real-world cohort describes longitudinal ROS1 management with evolving treatments. Favourable survival likely reflects reflex molecular testing, access to ROS1i, and high clinical trial enrolment.

In alignment with the mRNA findings, the phospho-kinase array results expose variant-mediated signaling events that were not previously linked with the functionality of CD74-ROS1. Taken altogether, this study provides an innovative view of CD74 as a fusion partner in CD74-ROS1 and contributes a list of novel molecular targets for mechanistic analysis and drug development.

The most frequently mutated genes were TP53, KRAS, EGFR, and STK11, with no significant differences between groups; ROS1 alterations were absent in STAS-negative tumors but detected more frequently in STAS-positive cases. Overall, these findings indicate that STAS positivity is associated with high-risk histological subtypes and advanced disease, suggesting its importance as a marker of tumor aggressiveness and emphasizing the need for its systematic evaluation in lung adenocarcinoma to better guide surgical planning and patient risk assessment.

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...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.

Rare actionable genomic alterations are recurrently identified in NGS-assessed NSCLC cohorts. These findings support the clinical value of broad genomic profiling, provide realistic expectations for diagnostic yield in routine practice, and may inform precision oncology implementation, molecular-testing pathways, and resource allocation.