ALK

Homozygous MTAP loss is frequently observed in oncogene-driven non-small-cell lung cancers (NSCLC), particularly in EGFR, ALK, and RET altered subtypes. While this loss did not significantly impact the response to first-line targeted therapies, it creates a selective vulnerability to PRMT5 inhibitors. Preclinical studies demonstrated that the PRMT5 inhibitor BMS-986504 is active in MTAP-deleted NSCLC models and can enhance the efficacy of existing targeted therapies. These findings suggest a novel combined therapeutic strategy for NSCLC patients with MTAP loss.

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.

This study investigated oncogenic fusions in 11 unclassified pulmonary spindle cell tumors, aggressive neoplasms with limited treatment options. Using anchored multiplex PCR-based targeted RNA sequencing, researchers identified ALK gene fusions in two patients (18.2%), specifically PPFIBP1::ALK and SYCL3::ALK. Both tumors also exhibited positive ALK immunohistochemical staining, despite showing morphological heterogeneity. These findings expand the molecular spectrum of these rare tumors and highlight the importance of detecting ALK fusions, including those with uncommon partners.