NTRK and Cancer — Tumor-Agnostic Fusion Drivers, Neurotrophin Signaling, and High-Impact Targeting

NTRK refers to a family of genes encoding tropomyosin receptor kinases (TRKs):
-NTRK1
-NTRK2
-NTRK3

Physiologically, TRKs are activated by neurotrophins (NGF, BDNF, NT-3) and regulate neuronal survival, differentiation, and synaptic plasticity.

Direction of Regulation in Cancer
-Kinase signaling: STRONGLY UPREGULATED
-Not via overexpression or point mutation, but via fusion-mediated activation
This makes NTRK fusions among the cleanest examples of oncogenic addiction.

NTRK fusions are rare overall but highly actionable:
-Tumors with NTRK fusions often show dramatic and durable responses to TRK inhibitors
-Efficacy is independent of tissue of origin
This led to tumor-agnostic drug approvals, a major paradigm shift in oncology.

Cancer Types Where NTRK Fusions Are Seen
Frequency	            Examples
High (defining event)	    Secretory breast carcinoma, congenital fibrosarcoma, infantile fibrosarcoma
Low (but actionable)	    Lung, colorectal, thyroid, melanoma, sarcoma, glioma

Because prevalence is low in common cancers, screening strategy matters.

NTRK is therefore a low-frequency, ultra-high-impact biomarker