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How NTRK Genes Function in NSCLC May Offer Clues to Appropriate Therapeutic Strategies

By: Kayci Reyer
Posted: Friday, May 20, 2022

Research presented in Frontiers in Oncology describes the function of, diagnostic techniques for, and treatment options for NTRK gene fusion–positive non–small cell lung cancer (NSCLC). Qian Chu, MD, PhD, of Huazhong University of Science and Technology, Wuhan, China, and colleagues noted that although NTRK fusions are rare in this cancer type, understanding how NTRK genes function in patients with NSCLC may help clinicians to better understand resistance to therapy and how best to improve outcomes.

The study found that NTRK gene fusion, known to be a driver of many types of solid tumors, could not be linked to some clinical features in NSCLC. NTRK fusion has not been found to coexist with other canonical mutations such as KRAS, EGFR, ALK, or ROS1. Although first-generation TRK inhibitors have been effective in patients with locally advanced or metastatic disease plus NTRK fusions, treatment resistance eventually develops via secondary mutations in the kinase domain and bypasses signaling activation. Therefore, next-generation TRK inhibitor treatment targets those resistance mechanisms.

Of note, patients receiving epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) may develop resistance via NTRK fusion; these patients may benefit from undergoing a combination therapy of EGFR-TKIs plus TRK inhibition. Effective therapeutic practices for patients with NSCLC may be identified by detecting the presence of NTRK fusions, secondary mutations, and/or activated bypass signaling.

“In terms of immunotherapy, no response was observed in two cases with NSCLC, the efficacy of [immune checkpoint inhibitors] in patients with NTRK fusion has not been well described, and whether combination of TRK inhibitors with [immune checkpoint inhibitors] possesses better efficacy and safety is not yet clear, thus, further investigation is urgently required to address these issues more fully,” concluded the authors.

Disclosure: The study authors reported no conflicts of interest.

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