ROS1

This article highlights the significance of rare and ultrarare gene fusions, beyond established ones like ALK and ROS1, in lung cancer. It emphasizes that emerging fusions, involving receptor tyrosine kinases or their ligands, such as EGFR-SHC1, unveil novel mechanisms of oncogenic activation. These discoveries are propelling precision medicine towards an era of "ultraprecision" oncology, enabling increasingly individualized treatment strategies for cancer patients.

This Australian multicenter study, derived from the AURORA registry, analyzed real-world treatment sequencing and survival in 115 patients with ROS1-rearranged NSCLC between 2012 and 2025. It revealed that a majority of patients (74%) received a ROS1 inhibitor as first-line therapy, with increasing use of later-generation inhibitors. Median overall survival was 56 months, extending to 80 months for those treated with a later-generation ROS1 inhibitor in the first line. Brain metastases and high PD-L1 expression were associated with shorter overall survival.

This study characterized the genomic landscape of leiomyosarcoma, a rare and aggressive tumor, by analyzing a large dataset from the AACR Project GENIE. Researchers examined over 1,000 tumor samples, identifying the most frequent somatic mutations and copy number alterations. TP53, RB1, and ATRX were the most commonly altered genes, with homozygous deletions of RB1 and TP53, and MAP2K4 amplifications. The study also highlighted enriched IGF2 and AXIN1 alterations in metastatic samples, suggesting their potential role in disease progression. These findings enhance the understanding of leiomyosarcoma biology and could guide future precision oncology strategies.

This retrospective study analyzed 120 cases of lung adenocarcinoma (LUAD) with malignant serous effusions (MSE) to characterize their clinicopathologic, molecular, and prognostic features. Pleural effusions were most common, but pericardial involvement was associated with the shortest overall survival. Molecular profiling revealed TP53 mutations and actionable alterations in genes such as EGFR, KRAS, BRAF, ALK, and ROS1. NKX2-1 (TTF-1) negativity and the absence of actionable alterations were independent adverse prognostic factors, with dual NKX2-1/CD274 (PD-L1) negativity defining the poorest prognosis subgroup. Immunotherapy-based regimens and tyrosine kinase inhibitors showed varying survival benefits.