ROS1 fusion

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.

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.

The efficacy of tyrosine kinase inhibitors (TKIs) crizotinib, ceritinib, lorlatinib, entrectinib, and repotrectinib was systematically evaluated. Our findings underscore that although G2032R and L2026M mutations reside within the kinase active site, their impact extends far beyond steric hindrance, altering overall kinase domain dynamics. Collectively, these data establish a robust panel of patient-derived ROS1 cell lines that recapitulate clinical resistance patterns and, together with complementary computational modeling, provide a valuable framework to dissect ROS1 tumor biology and support rational design of next-generation inhibitors.

P2/3, N=396, Not yet recruiting, Shanghai Chest Hospital

P1/2, N=358, Recruiting, Xilio Development, Inc. | Trial completion date: Feb 2027 --> Sep 2028 | Trial primary completion date: Feb 2027 --> Sep 2028

We present the case of a 60-year-old non-smoking woman previously treated for luminal B human epidermal growth factor receptor 2 (HER2)-positive invasive breast carcinoma with surgery, AC60 chemotherapy, trastuzumab, breast radiotherapy, and hormone therapy at the Mohammed VI Oncology Center in Casablanca, Morocco. The patient received neoadjuvant vinorelbine-cisplatin chemotherapy followed by volumetric modulated arc therapy (VMAT) thoracic radiotherapy at 66 Gy, achieving clinical and radiological stabilization. This case highlights the occurrence of a second driver-negative primary lung adenocarcinoma in a non-smoker and underscores the importance of integrated histopathological, immunohisto chemical, and targeted molecular evaluation in distinguishing primary tumors from metastases, as well as the potential role of post-therapeutic carcinogenesis.

We report the case of a 61-year-old woman diagnosed with stage IV lung adenocarcinoma with brain metastasis harboring an EGFR exon 19 deletion (p.E746_A750del), who acquired resistance to osimertinib through a ROS1 fusion bypass pathway. The patient achieved a survival of over 6.5 years from initial diagnosis through ongoing adjustments to targeted therapy, including sequential treatment with crizotinib, entrectinib, and lorlatinib...Notably, we observed an interesting phenomenon with both crizotinib and entrectinib: while initial treatment led to intolerable adverse reactions requiring discontinuation, subsequent reintroduction of the same agent was well-tolerated. This case report aims to provide potential treatment strategies for patients with similar complex co-mutations.

P2, N=152, Not yet recruiting, The Third Xiangya Hospital of Central South University

P1/2, N=67, Recruiting, D3 Bio (Wuxi) Co., Ltd | Active, not recruiting --> Recruiting | Trial completion date: Apr 2028 --> Aug 2028 | Trial primary completion date: Apr 2028 --> Aug 2028

P2, N=277, Active, not recruiting, Daiichi Sankyo | Trial completion date: Jul 2026 --> Jan 2027

P2, N=32, Not yet recruiting, University of Washington | Initiation date: Jun 2026 --> Sep 2026