Sensitivity to Entrectinib Associated With a Novel LMNA-NTRK1 Gene Fusion in Metastatic Colorectal Cancer

摘要: In metastatic colorectal cancer (CRC), actionable genetic lesions represent potential clinical opportunities. NTRK1, 2, and 3 gene rearrangements encode oncogenic fusions of the tropomyosin-receptor kinase (TRK) family receptor tyrosine kinases in different tumor types. The TPM3-NTRK1 rearrangement is a recurring event CRC that renders tumors sensitive to TRKA inhibitors preclinical models. We identified abnormal expression protein liver metastases patient refractory standard therapy. Molecular characterization unveiled novel LMNA-NTRK1 within chromosome 1 with potential, was treated pan-TRK inhibitor entrectinib, achieving partial response decrease hepatic target from 6.8 8.2cm longest diameter 4.7 4.3cm, respectively. To our knowledge, this first evidence efficacy for therapeutic inhibition solid tumor, illuminating genomic-driven strategy identify CRCs reliant on oncogene be clinically targeted entrectinib.