NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3)

mIHC analysis indicated reduced Th1 but increased Th2 and Th17 biomarkers in MSI-H CRC. This study identified key genes and immune microenvironment alterations regulated by hsa-miR-99a in CRC, offering novel insights and potential therapeutic targets for CRC treatment.

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.

P1/2, N=28, Active, not recruiting, Bicycletx Limited | Recruiting --> Active, not recruiting

Additionally, MYCN-induced miR-221 was found to suppress CREB expression. Together, these findings demonstrate MYCN-dependent effects of TrkC signalling and highlight the therapeutic potential of targeting the PKA pathway to induce differentiation in high-risk MYCN-amplified neuroblastoma.

NTRK-fusion defines a distinct PTC molecular subtype characterized by a high burden of LNM and a spectrum of features linked to follicular growth patterns. These findings facilitate the preoperative identification of this tumor subtype and provide a foundation for individualized risk stratification and tailored management strategies.

The patient was treated with VAC chemotherapy (vincristine, actinomycin D, cyclophosphamide), local radiotherapy (60 Gy), cranial prophylactic radiotherapy (12 Gy), and subsequent debulking surgery. Multimodal treatment incorporating chemotherapy, radiotherapy, surgery, and targeted maintenance therapy can achieve meaningful disease control in aggressive craniofacial MCS. To our knowledge, this represents one of the very few reported pediatric cases of maxillary MCS with confirmed HEY1::NCOA2 fusion managed with sirolimus-based maintenance therapy.

In contrast, combined HCC-CCA (n=4) displayed oncogene alterations in known targets (TP53, BAP1 and TERT). Increased atypical ductular reactions in specimens of HCC-patients after transarterial embolization treatment can be identified as regenerative phenomenon with distinct morphology and immunophenotype.

P=N/A, N=40, Enrolling by invitation, Chang Gung Memorial Hospital | Not yet recruiting --> Enrolling by invitation

Two relapsed patients received salvage chemotherapy [vincristine-actinomycin D-cyclophosphamide (VAC) or ifosfamide-carboplatin-etoposide (ICE)], which showed limited efficacy. One relapsed patient with TPM3::NTRK1 received larotrectinib but died two months later; another with EGFR-KDD experienced disease stabilization after afatinib plus programmed cell death protein 1 (PD-1) blockade following progression on entrectinib and anlotinib...While most patients experienced favorable outcomes following surgery, relapsed cases highlight the challenges associated with molecularly atypical disease. These observations are descriptive in nature and underscore the need for larger collaborative studies to better define prognostic factors and optimal management strategies in CMN.

We also extensively review the existing literature and summarize the clinicopathological features, molecular profiles, and treatment implications of this report. Given the availability of effective TRK inhibitors, it is imperative to consider NTRK-rearranged sarcoma in the differential diagnosis of spindle cell sarcomas of the lower genital tract.

Cases of malignant peripheral nerve sheath tumours are, in contrast to desmoplastic melanoma S‑100 protein negative or express this marker only focally, and show a decreased nuclear expression of H3K27. Desmoplastic melanoma shows a focal nuclear expression of p53 in contrast to neurofibroma.

Tumors harboring these fusions respond dramatically to TRK inhibitors (e.g., larotrectinib, entrectinib, and repotrectinib), which selectively target the constitutively active fusion protein. Conclusively, this first report of three novel NTRK2 fusion transcript variants co-occurrence in an MTC patient expands the known spectrum of translocation partners in NTRK2 rearrangements. Prospective validation of their impact on TRK-targeted therapy efficacy and disease prognosis requires long-term follow-up.