NTRK
🧬 NTRK1, NTRK2, NTRK3 (Neurotrophic Tyrosine Receptor Kinases)
🔍 What are NTRK genes?
The NTRK family consists of three genes—NTRK1, NTRK2, and NTRK3—which encode the receptor tyrosine kinases TRKA, TRKB, and TRKC, respectively. These receptors normally regulate neuronal development and function by binding neurotrophins.
📊 Prevalence of NTRK Alterations in Cancer
- NTRK alterations primarily occur as gene fusions involving NTRK1/2/3 fused with various partner genes.
- These fusions lead to constitutive activation of the kinase domain and oncogenic signaling.
- Prevalence:
- Rare overall (<1% in common cancers) but found across many tumor types.
- More frequent in certain rare cancers:
- Infantile fibrosarcoma
- Secretory breast carcinoma
- Mammary analogue secretory carcinoma (MASC) of salivary glands
⚙️ Mechanism of Oncogenic Activation
- NTRK gene fusions generate chimeric proteins with constitutive kinase activity.
- This activates downstream signaling pathways including:
- RAS-RAF-MEK-ERK (MAPK) pathway
- PI3K-AKT-mTOR pathway
- PLCγ pathway
- Leads to uncontrolled cell proliferation, survival, and differentiation block.