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.

Concurrent targeting of PI3K and IR/IGF-1R signaling effectively overcomes adaptive resistance in PIK3CA-mutant NSCLC, supporting the rationale for further clinical evaluation of this combined therapeutic strategy.

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.

We deployed our workflow to study schwannoma development and to test two clinically relevant drugs (rapamycin and brigatinib) head-to-head. Our results uncovered the very early onset of heterogeneity and macrophage recruitment to initiating schwannomas, and the unexpectedly distinct impacts of the two drugs on both, highlighting the value of the pipeline for rapid, innovative future drug-testing.

Oncogenic RET gene rearrangements drive a subset of lung adenocarcinomas (LUAD) and the tyrosine kinase inhibitors (TKIs) selpercatinib and pralsetinib are approved therapeutics. By contrast, upfront treatment with selpercatinib and crizotinib in orthotopic tumors yielded complete elimination of 7 of 9 TR.1 tumors and both deepened and prolonged the duration of response in TR.2 tumors. The findings provide new insight into mechanisms of acquired resistance through bypass signaling and highlight the therapeutic benefit of simultaneous upfront blockade of driver oncogenes and dominant resistance mechanisms in LUAD.

P1/2, N=20, Recruiting, Tang-Du Hospital | Not yet recruiting --> Recruiting

This over-a-decade-long clinical development program led to the commercialization of a palatable, dose-flexible, oral solid multiparticulate pediatric formulation of crizotinib for patients with anaplastic large cell lymphoma or inflammatory myofibroblastic tumors. The clinical outcomes and development strategy described herein provide a practical framework to support future pediatric formulation development programs.

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.

ALK+ squamous and adenosquamous NSCLCs are rare, but biologically distinct, with inferior outcomes on 1L ALK TKI, highlighting the need for further research to develop effective treatment strategies.

Small-molecule ALK inhibitors, including crizotinib, have demonstrated high overall response rates (67%-88%) and complete remission rates (~60%-80%) in relapsed or refractory ALK-positive ALCL, often with rapid clinical responses...In addition, it explores emerging strategies for integrating ALK inhibitors into precision-based management of T-cell lymphomas, including combination approaches with chemotherapy, immunotherapy or antibody-drug conjugates. Collectively, these developments highlight a paradigm shift towards biology-driven, personalized therapy in ALK-positive ALCL.

P=N/A, N=97, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting | Trial completion date: Mar 2027 --> Nov 2026 | Trial primary completion date: Mar 2027 --> Nov 2026

This case highlights the importance of genetic profiling and rapid and substantial efficacy of alectinib in treating ALK-positive PLADC, reinforcing the role of ALK inhibitors in managing severe cases and offering valuable insights for clinical strategies.