NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1)

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.

This case highlights the power of comprehensive molecular profiling and high-frequency ctDNA monitoring to capture tumor evolution and minimal residual disease. Importantly, it further demonstrates how MRD-guided surveillance enables a precise balance between fast-acting targeted therapy and the sustained effects of immunotherapy, providing a blueprint for individualized, context- driven treatment strategies in rare molecular subtypes of pancreatic cancer.

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

P2/3, N=230, Not yet recruiting, Swiss Cancer Institute | Initiation date: Dec 2025 --> Jul 2026

Only one patient died 16 months after surgery due to an unrelated traffic accident.

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.

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.

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.

OFA balances TAT, QNS, and detection, whereas SO-NGS offers comprehensive detection with longer TAT and higher QNS. An optimized assay combining SGP's speed, OFA's reliability, and SO-NGS's comprehensiveness could improve outcomes.

Of 77 unique panels evaluated, only 5 captured all recommended biomarkers for mNSCLC. Ensuring targeted panels assess all relevant biomarkers is crucial for optimal patient treatment.

Inhibitors such as larotrectinib, entrectinib and repotrectinib are used when cancer cells harbor NTRK1, NTRK2 or NTRK3 fusion...Short courses of prednisone for the former and dexamethasone for the latter were initiated after failure of standard analgesia... For patients experiencing TRK inhibitor withdrawal pain, especially when tapering down the inhibitor is not an available strategy, a short course of corticosteroids can provide lasting relief. These cases emphasize the importance of better understanding the mechanism underlying the relationship between NRTK, NGF and nociception.