RET

Results from the LIBRETTO-432 study indicate that adjuvant selpercatinib substantially improves event-free survival in patients with early-stage RET fusion-positive non-small cell lung cancer (NSCLC). This finding establishes selpercatinib as a new standard of care for this rare disease. Nevertheless, challenges persist regarding patient identification and access to RET fusion screening.

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 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.