NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3)

These findings highlight the value of RNA-based NGS, particularly when used alongside DNA NGS, to provide a comprehensive assessment of NTRK fusions and co-occurring gene alterations. Implementation of combined DNA and RNA CGP in a community health system setting enables detection of both known and novel NTRK fusions and can inform clinical care of cancer patients.

P2, N=73, Active, not recruiting, BicycleTx Limited | Recruiting --> Active, not recruiting

We discuss advanced three-dimensional and organoid-based models that recapitulate niche-specific regulation of the Trk axis and evaluate emerging therapeutic strategies combining epigenetic modulators, differentiation-inducing agents, and RTK-targeted compounds. Understanding the temporal and spatial dynamics of Trk signalling may open new opportunities to therapeutically stabilise differentiation states and disrupt adaptive resistance programs in high-risk NB.

IL1RAP expression rendered these malignancies similarly vulnerable to IL1RAP-targeting ADCs, which effectively blocked growth of ALCL xenografts and syngeneic ETV6-NTRK3+ sarcomas. Lack of detectable normal tissue toxicity, including in non-human primates, support the further clinical translation of IL1RAP-targeting ADCs.

Patients in cluster 1 may benefit from anti-nucleotide repair therapies such as platinum therapy, radiotherapy, targeting of fibroblasts, and targeting of NTRK3, while patients in cluster 2 may benefit from immunotherapy, antiangiogenic therapy, targeting of lipid metabolism, and targeting of EGFR. This study may offer novel insights into improving the overall prognosis of patients with LUAD by leveraging molecular subtype-based precision therapy, as demonstrated by recent advancements in the identification of prognostic biomarkers and therapeutic targets.

Functional NTRK fusion-positive tumors comprise biologically and clinically distinct subsets defined by tumor type and MSI/TMB context. Concurrent reporting of MSI/TMB (and HRD/EBV when available) together with NTRK fusion status may facilitate integrated clinical interpretation, support precision treatment selection, and refine trial stratification in clinical practice.

P2, N=32, Completed, The University of Sydney | Active, not recruiting --> Completed

This study highlights the importance of targeted NGS combined with FISH and clinicopathological analysis for accurate diagnosis in NTRK fusion PTC. While pan-TRK IHC is useful for initial screening, confirmatory NGS is essential to avoid false-negative results.

Combination therapy with osimertinib and entrectinib induced regression of pulmonary lesions, but the patient ultimately discontinued all targeted agents due to the development of severe hepatorenal failure and Escherichia coli-associated sepsis. This case highlights the need for additional research into the safety profile of EGFR-TKI/NTRK inhibitor combination regimens in resistant NSCLC.

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