NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1)

P2, N=534, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Dec 2025 --> May 2026 | Trial primary completion date: Dec 2025 --> May 2026

A higher rate of CDx SV detection-most significantly for NRG1 and NTRK fusions-was observed using concurrent DNA-CGP and RNA-CGP compared to DNA-CGP alone. Our results highlight the complementary nature of these methods. Given the substantial clinical benefit of SV targeted therapies, an integrated DNA/RNA profiling strategy should be part of routine clinical care.

P2, N=78, Completed, Anhui Provincial Hospital | Recruiting --> Completed

While prognosis steadily improved with age, mutation status remained the dominant factor determining outcomes. Somatic drivers offer prognostic insights independent of age in paediatric and young adult DTC, establishing a molecular framework for precision risk stratification that complements traditional clinical staging and age-based assessments.

Based on these molecular findings, the diagnosis was confirmed as an NTRK-rearranged high-grade sarcoma with an unusual histomorphological phenotype. This case highlights novel molecular characteristics of NTRK-rearranged high-grade sarcoma and underscores the critical role of comprehensive molecular profiling in diagnosing challenging cases.

The results demonstrated that overexpression of KDM3B in CRC could inhibit H3K9me2, which in turn contributed to the upregulation of TrkA, enabling binding of nerve growth factor (NGF) to it and ultimately inducing CRC NI. The present study reveals the intrinsic mechanism of NI in CRC, which lays a solid theoretical foundation for using KDM3B as a prognostic indicator and therapeutic target for CRC.

KRAS G12V-mutated NSCLC is characterized by a strong association with tobacco use, high co-mutation rates in clinically relevant genes, and a favorable response to PD-L1-based immunotherapy. The observed mutation landscape supports the potential for dual checkpoint blockade in a significant subset.

Through integrated histopathological, immunohistochemical, and molecular analyses, we characterize the diagnostic nuances, biological behavior, and potential drivers of progression in this entity. Our findings expand the morphological and clinical spectrum of LMNA::NTRK1-rearranged tumors and highlight the need for close follow-up and consideration of adjuvant targeted therapy in high-risk cases.

The lung metastases appeared as multiple nodules with irregular or smooth margins in both lungs and showed variable FDG uptake, ranging from low-grade to high-grade activity, which may reflect different biologic behavior of these tumors. The lung tumors disappeared or decreased significantly in size after tropomyosin receptor kinase inhibitor therapy.

Larotrectinib was used in 142 patients, demonstrating an 83.80% response rate, with low mortality (2.82%) and recurrence (2.11%) rates. Entrectinib had a lower response rate of 63.64%. We confirm the rarity of NTRK1-3 fusions in sarcomas. TRK inhibitors show high efficacy in sarcomas, emphasizing the necessity of genomic testing in all cases.Protocol registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024563594.

P1/2, N=242, Recruiting, VM Oncology, LLC | Phase classification: P1 --> P1/2 | N=82 --> 242 | Trial completion date: Jun 2027 --> Jun 2028 | Trial primary completion date: Dec 2026 --> Dec 2027

This case underscores the importance of integrating molecular diagnostics into the evaluation of atypical spindle cell tumors, particularly those presenting with aggressive clinical features despite low-grade histology. Early identification of NTRK fusions enables timely initiation of TRK inhibitor therapy, offering durable disease control and functional recovery. Broader awareness and implementation of molecular testing can greatly enhance the management of rare pediatric sarcomas.