NTRK (Neurotrophic receptor tyrosine kinase)

Entrectinib was administered, and an excellent response was observed. This case emphasizes the relevance of performing NGS in cases with unusual clinicopathological findings to identify potential treatment options. Importantly, the morphology deviated from the classic fibrosarcoma-like appearance described in most adult NTRK3-fused neoplasms and broadens the morphological spectrum in which these neoplasms should be considered.

P2, N=1, Terminated, University of Texas Southwestern Medical Center | N=52 --> 1 | Active, not recruiting --> Terminated; Sponsor decision to halt funding.

P1/2, N=420, Recruiting, BioNTech SE

P2, N=90, Recruiting, Lantern Pharma Inc. | Trial completion date: Jun 2026 --> Jun 2027 | Trial primary completion date: Dec 2025 --> Dec 2026

This study suggests that pathologic prescreening can enrich for targetable gene rearrangements in BRAF wild-type PTC and serve as a resource-sparing strategy before RNA sequencing. In prescreened cases, ALK IHC performed well, while pan-TRK and RET IHC had limitations.

Precision diagnostics now encompass next-generation sequencing (NGS)-based comprehensive genomic profiling, enabling identification of actionable alterations such as PIK3CA mutations, HER2 amplification, BRCA1/2 pathogenic variants, and NTRK fusions, each linked to approved therapeutic agents. The purpose of this review is to provide a comprehensive synthesis of current and emerging diagnostic modalities in breast cancer-from population-level screening to individualized molecular profiling-and to examine how integrative, multimodal diagnostic platforms are reshaping clinical decision-making in the era of precision medicine.

Particularly, the detection sensitivity for NTRK3 fusions was significantly enhanced and reached 95.89 %. This study contributes to clarifying NTRK fusion distribution in patients and validates a standardized, sensitive pan-TRK IHC strategy for clinical screening.

P2, N=28, Not yet recruiting, Shanghai Juncell Therapeutics

P2, N=243, Recruiting, Shanghai Henlius Biotech | N=41 --> 243

Targeted therapies with TRK inhibitors (TRKi), including larotrectinib and entrectinib, have shown promising efficacy with rapid and durable responses for patients with LGGs and HGGs. Overall, TRKi represent a significant advance for treating NTRK fusion-positive CNS tumors, especially in pediatric populations, offering new hope for patients with limited treatment options. Further studies are required to optimize their use and address unresolved challenges.

Global programs like the WHO Global Initiative for Childhood Cancer and the ATOM Coalition play a vital role in improving drug access and policy advocacy. Enabling precision medicine in LMICs calls for a coordinated multi-stakeholder approach, including integration into the national cancer care policy, and is critical to bridging the survival gap and ensuring equitable outcomes for children with brain tumors globally.

P=N/A, N=825, Active, not recruiting, Dana-Farber Cancer Institute | Trial primary completion date: Jan 2026 --> Jun 2026