Non Small Cell Lung Cancer

PACIFIC-5 met its primary endpoint of improved PFS after either cCRT or sCRT. Follow-up for overall survival is ongoing.

This real-world study suggests that MET overexpression, as assessed by IHC, is associated with better survival in advanced NSCLC patients treated with ICIs, independent of PD-L1 level. These results suggest the potential of MET expression as a predictive marker for ICI efficacy in advanced NSCLC patients and support the combination of MET-targeted agents with anti-PD1/PD-L1 ICIs as a promising strategy for NSCLC patients with MET overexpression.

Currently, selpercatinib, larotrectinib, and repotrectinib are approved by the FDA for the treatment of certain solid tumors harboring specific gene fusions. Recent studies on zenocutuzumab resulted in the FDA-accelerated approval for NGR1 fusion-positive NSCLC and PDAC. Germline mutations may specifically increase responsiveness to poly(ADP-ribose) polymerase (PARP) inhibitors or platinum-based treatments. Comprehensive genomic profiling, incorporating fusion detection and germline testing, is essential to identify patients who may benefit from precision-based approaches.

Finally, qRT-PCR revealed significant downregulation of EMT-related genes vimentin and N-cadherin, along with the EMT transcription factor Twist. These findings highlight soluble FDLT-derived biomolecules as a potential tool to design alternative treatment strategies for NSCLC.

Regulation of SOX18 by miR-24-3p highlights a potential therapeutic vulnerability. These findings underscore the significance of SOX transcription factors as biomarkers and potential targets for novel treatment strategies in NSCLC.

Additional discussion includes advancements in therapies directed at MET, HER2, RET, ROS1, and FGFR alterations-each representing promising targets in NSCLC. This review concludes by exploring the growing evidence surrounding TROP-2 as a novel therapeutic target, especially relevant in cases where previous targeted treatments have failed.

Among the 18 RET fusion-positive samples, one was identified as an extremely rare case (RUFY3::RET), and two were determined to be novel fusions (FN1::RET, PPP1R21::RET). The findings of this study demonstrate that exon coverage imbalance analysis serves as a robust complement to computational RNA-seq analysis pipelines for the detection of clinically relevant RET fusions.

According to the European Society for Medical Oncology guidelines for non-oncogene-addicted metastatic non-small-cell lung cancer (NSCLC), patients with metastatic squamous-cell carcinoma (LUSC) or metastatic non-squamous NSCLC with performance status 2 and PD-L1 < 50% may receive single-agent chemotherapy with gemcitabine (GEM), docetaxel (DOC), or vinorelbine. Analysis of three key long non-coding RNAs (lncRNAs)-MALAT1, NEAT1, and HOTAIR-showed variable expression in the studied cell lines as a potential response to DOC and GEM treatment. Our findings indicate different cellular effects of GEM and DOC in NSCLC cell lines and provide an overview of how currently used chemotherapeutics may influence the expression of lncRNAs.

P2, N=74, Not yet recruiting, Università Vita-Salute San Raffaele

P1, N=168, Completed, AbbVie | Active, not recruiting --> Completed | Trial completion date: Jun 2025 --> Sep 2025 | Trial primary completion date: Jun 2025 --> Sep 2025

P1, N=188, Recruiting, Alterome Therapeutics, Inc. | N=130 --> 188

P2, N=24, Active, not recruiting, Shanghai Pulmonary Hospital, Shanghai, China