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Oncogenic NTRK1 rearrangement identified in lung cancer
Researchers have identified a novel and potentially clinically actionable oncogenic gene fusion in patients with lung cancer harboring the kinase domain of the NTRK1 gene that encodes the TRKA protein.
“Our understanding of cancer complexity is increasing, and lung cancer continues to be dissected into a series of uncommon or even rare diseases based on the molecular alterations driving a patient’s individual cancer,” researcher Vincent Miller, MD, chief medical officer at Foundation Medicine in Boston, said in a press release.
Vincent Miller
To categorize additional possible drug-sensitive oncogenes in lung cancer, researchers from Foundation Medicine, the University of Colorado Cancer Center and Dana-Farber Cancer Institute used the “FoundationOne” assay to evaluate cancer-related genes on tumor samples from patients who were negative for activating alterations in EGFR, KRAS, ALK and ROS1 using standard clinical assays.
Preclinical data demonstrated that treatment of cells expressing NTRK1 fusions with inhibitors of TRKA kinase activity — ARRY-470, CEP-701 and crizotinib (Xalkori, Pfizer) — inhibited tumor growth. However, only one patient harboring the MPRIP-NTRK1 fusion demonstrated a minor radiographic response to crizotinib.
In the study, three of 91 patients (3.3%) without known oncogenic alterations profiled by the FoundationOne assay were to found to harbor an NTRK1 gene fusion.
“By discovering a new and potentially clinically actionable gene fusion in lung cancer, we believe this is an opportunity to explore new and different treatment options for patients harboring this fusion,” Miller said. “Based on these findings, we believe clinical studies of selective TRK inhibitors in NTRK1 rearranged non–small cell lung cancer are warranted.”
Disclosure: Two researchers report they are listed on a regularized patent application filed with the US Patent and Trademark Office related to NTRK1 as a predictive biomarker in cancer.