Notably, Entrectinib ameliorated LPS-induced memory impairments in vivo. Collectively, these findings indicate that Entrectinib attenuates neuroinflammation and improves memory performance, supporting its potential therapeutic relevance for neuroinflammation-associated cognitive disorders.

Drug likeness analysis results revealed that chalcone derivatives CD5, CD8, and CD9 and reference standard drugs lorlatinib and topotecan showed no violations against all five drug likeness rules. Current study overcomes these challenges by employing green nanocatalysts (Al(OH)₃ and Ti/Fe@Al(OH)₃) for eco-friendly, high-yield synthesis and computational screening to design potent, multi-target lung cancer therapeutic chalcone compounds. The online version contains supplementary material available at 10.1007/s40203-026-00599-3.

Owing to the presence of neural tissue, NTRKs are highly positive in IHC, making these genes unsuitable as biomarkers for assessing NTRK inhibitor sensitivity and resistance, which are tissue-agnostic drugs. The observed low fusion rate is consistent with the literature, and the significance of the numerous point mutations identified as agnostic markers warrants further investigation. NTRK expression, fusion, and point mutations were not associated with clinical parameters or survival.

P1, N=30, Completed, Bristol-Myers Squibb | Recruiting --> Completed

These studies demonstrate that NTRK wild-type receptors are important drivers of brain metastatic colonization and progression in different subtypes of lung cancer, independent of their driver alterations. Thus, they provide rationale to expand the use of FDA-approved NTRK inhibitors with brain penetrance for the prevention of CNS metastases.

We report a 19-year-old male with ALK-rearranged, radioiodine-refractory PDTC who started systemic therapy with ceritinib, achieving a complete metabolic response. Treatment with the third-generation ALK inhibitor led to a deep and durable complete metabolic response, sustained for more than four years, including persistence of remission after treatment discontinuation, with minimal toxicity. This case highlights the potential role of sequential ALK inhibition to overcome acquired resistance in ALK-rearranged TC and underscores the importance of comprehensive molecular profiling to guide personalized treatment strategies in rare aggressive thyroid cancers.

This TPR-ALK fusion-driven IMT demonstrates that disease progression after an initial response to crizotinib can be effectively overcome with lorlatinib, resulting in rapid and durable clinical benefit. These findings add to emerging evidence supporting next-generation ALK inhibitors as effective treatment options for ALK-rearranged IMT after crizotinib failure.

Peripheral monocyte profiling of the patient post-Repotrectinib and localized radiotherapy showed 75% CD8+/CD3 + T cells, 14.2% CD4+/CD3 + T cells, 3.95% regulatory T cells (Tregs), and 38% PD-1 + CD3 + T cells...Furthermore, we also provide a comprehensive review of recent clinical advancements in ALK/ROS1-TKI for NSCLC, including mechanistic insights into TKI resistance development. This case underscores the therapeutic potential of molecular-targeted agents in LUSC and highlights the essential role of NGS-guided precision oncology.

Although PCNSTL is exceptionally rare, we identified distinct neuroimaging patterns showing highly aggressive features on MRI but hypometabolic PET imaging, which may assist in identifying future PCNSTL cases. Despite the limited cohort size, our findings suggest that MTX-based chemotherapy with ASCT may translate into favorable outcome. We report on an ALK1-positive PCNSTL case with sustained complete remission after targeted therapy with lorlatinib.

P1, N=15, Recruiting, Nationwide Children's Hospital | Active, not recruiting --> Recruiting

Lorlatinib, a third-generation ALK tyrosine kinase inhibitor, was started which showed significant disease regression at 18-month follow-up. This report highlights the favorable response to targeted ALK inhibition in central nervous system ALK-positive histiocytosis.