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ALK, ROS1 and now NTRK1: Study shows prevalence of new genetic driver in lung cancer
Date:5/31/2014

A University of Colorado Cancer Center study presented at the 50th Annual Meeting of the American Society for Clinical Oncology (ASCO) draws a line from mutation of the gene NTRK1, to its role as an oncogene in non-small cell lung cancer, to treatment that targets this mutation. The current study reports the prevalence of the NTRK1 mutation in an unselected population of 450 lung cancer samples, with >1% percent of patients testing positive. This and other work from Dr. Doebele's group forms the basis of a phase 1 clinical trial targeting NTRK1 mutations in advanced solid tumors (NCT02122913).

"Everything we know about lung cancer points to the idea that when we find one of these genetic drivers and can target it with a drug, patients will respond and tend to have a good amount of time on drug before it becomes ineffective. Obviously we can't guarantee the effectiveness of targeting the NTRK1 mutation at this point, but everything we know about these kinds of genes makes us extremely hopeful," says Robert C. Doebele, MD, PhD, investigator at the CU Cancer Center and associate professor of Medical Oncology at the CU School of Medicine.

Previous work in collaboration with Pasi A. Jnne, MD, PhD from the Dana-Farber Cancer Institute, examined lung cancer tumor samples from 36 "pan-negative" patients, meaning that no other driver oncogene had been identified. Next-gen sequencing at Foundation Medicine (Cambridge, MA) identified NTRK1 gene fusions as the potential driver in two of these samples.

Doebele and colleagues took the finding back to CU labs, where Marileila Varella-Garcia, PhD, developed a specific test for NTRK1 fusions based on fluorescence in situ hybridization (FISH), similar to what is currently used for ALK, ROS1 and RET fusions. This test would allow rapid detection of NRTK1 oncogenes in patient samples.

"But no one had ever looked for NTRK1 mutations in a large series of unbiased patient samples," Doebele says. "
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Contact: Erika Matich
erika.matich@ucdenver.edu
University of Colorado Denver
Source:Eurekalert

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