Squamous Cell Carcinoma, NOS

This study investigated the TP53 mutation landscape in oral squamous cell carcinoma (OSCC) and its association with patient survival. Using next-generation sequencing on 124 samples, pathogenic TP53 mutations were detected in 65% of patients, encompassing 75 distinct variant patterns. Patients harboring these mutations exhibited significantly shorter cancer-specific survival, particularly those with advanced-stage (III/IV) disease. Truncating or splice mutations were associated with an even worse prognosis. These findings highlight the importance of TP53-based molecular classification for developing novel precision strategies against OSCC.

This study investigates histologic transformation to lung squamous cell carcinoma (LUSC) in EGFR-mutant lung adenocarcinoma (LUAD) patients, an underrecognized resistance mechanism. Multiomic analyses revealed that patients with transforming or adenosquamous (LUAS) phenotypes experienced shorter overall survival on first-line osimertinib. Inactivation of the retinoblastoma (Rb) pathway, particularly via CDKN2A/B deletions, was identified as a key driver of this transformation. Furthermore, MET pathway upregulation was observed, and combined EGFR and MET inhibition demonstrated efficacy in preclinical models. These findings suggest novel strategies to counteract this aggressive form of resistance.