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- Title
Sensitivity to Entrectinib Associated With a Novel LMNA-NTRK1 Gene Fusion in Metastatic Colorectal Cancer.
- Authors
Sartore-Bianchi, Andrea; Ardini, Elena; Bosotti, Roberta; Amatu, Alessio; Valtorta, Emanuele; Somaschini, Alessio; Raddrizzani, Laura; Palmeri, Laura; Banfi, Patrizia; Bonazzina, Erica; Misale, Sandra; Marrapese, Giovanna; Leone, Antonella; Alzani, Rachele; Luo, David; Hornby, Zachary; Lim, Jonathan; Veronese, Silvio; Vanzulli, Angelo; Bardelli, Alberto
- Abstract
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 of receptor tyrosine kinases in different tumor types. The TPM3-NTRK1 rearrangement is a recurring event in CRC that renders tumors sensitive to TRKA kinase inhibitors in preclinical models. We identified abnormal expression of the TRKA protein in tumor and liver metastases of a CRC patient refractory to standard therapy. Molecular characterization unveiled a novel LMNA-NTRK1 rearrangement within chromosome 1 with oncogenic potential, and the patient was treated with the pan-TRK inhibitor entrectinib, achieving partial response with decrease in hepatic target lesions from 6.8 and 8.2cm in longest diameter to 4.7 and 4.3cm, respectively. To our knowledge, this is the first clinical evidence of efficacy for therapeutic inhibition of TRKA in a solid tumor, illuminating a genomic-driven strategy to identify CRCs reliant on this oncogene to be clinically targeted with entrectinib.
- Subjects
THERAPEUTIC use of monoclonal antibodies; COLON cancer treatment; METASTASIS; CANCER invasiveness; GENE fusion
- Publication
JNCI: Journal of the National Cancer Institute, 2016, Vol 108, Issue 1, p1
- ISSN
0027-8874
- Publication type
journal article
- DOI
10.1093/jnci/djv306