Case Report|Articles in Press, 100501

Primary Resistance to Larotrectinib in a Patient with Squamous Non-Small Cell Lung Cancer with Subclonal NTRK1 Fusion: Case Report

Open AccessPublished:March 17, 2023DOI:
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      The neurotrophic receptor tyrosine kinase (NTRK) genes encode the tropomyosin receptor kinase (TRK) proteins. NTRK fusions lead to constitutively active, ligand-independent downstream signaling. NTRK fusions are implicated in up to 1% of all solid tumors and 0.2% of non-small cell lung cancer (NSCLC). Larotrectinib, a highly selective small molecule inhibitor of all three TRK proteins, has a response rate of 75% across a wide range of solid tumors. Mechanisms of primary resistance to larotrectinib are not well understood. We report a case of a 75-year-old male with minimal smoking history with NTRK fusion-positive metastatic squamous NSCLC with primary resistance to larotrectinib. We suggest subclonal NTRK fusion as a possible mechanism contributing to primary resistance to larotrectinib.

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