NTRK fusions in lung cancer: From biology to therapy Review
| Authors: | Harada, G.; Santini, F. C.; Wilhelm, C.; Drilon, A. |
| Review Title: | NTRK fusions in lung cancer: From biology to therapy |
| Abstract: | Fusions involving TRK protein tyrosine kinases are oncogenic drivers in a variety of tumors in children and adults, with a prevalence of ∼0.2% in non-small cell lung cancer. Diagnosis can be challenging due to structural features such as NTRK intron length, but next-generation sequencing (NGS), including RNA-based NGS, increases detection. The first-generation TRK inhibitors, larotrectinib and entrectinib, have demonstrated clinically meaningful antitumor activity in TRK fusion-positive cancers in a tumor-agnostic fashion and should be considered first-line therapeutic options for TRK fusion-positive lung cancers. Furthermore, the first-generation TRK inhibitors are well tolerated. Care should be taken, however, to monitor on-target adverse events, such as dizziness, weight gain, paresthesias, and withdrawal pain. On-target and off-target mechanisms mediating TRK inhibitor resistance may occur. Next-generation TRK inhibitors, such as selitrectinib, repotrectinib, and taletrectinib, are available on ongoing clinical trials and address on-target resistance. This review will focus on NTRK fusions and TRK-directed targeted therapy specifically in the context of lung cancer. © 2021 Elsevier B.V. |
| Keywords: | nsclc; trk; ntrk fusions; trk fusion cancer; trk inhibitors |
| Journal Title: | Lung Cancer |
| Volume: | 161 |
| ISSN: | 0169-5002 |
| Publisher: | Elsevier Ireland Ltd. |
| Date Published: | 2021-11-01 |
| Start Page: | 108 |
| End Page: | 113 |
| Language: | English |
| DOI: | 10.1016/j.lungcan.2021.09.005 |
| PROVIDER: | scopus |
| PUBMED: | 34563714 |
| PMCID: | PMC8530887 |
| DOI/URL: | |
| Notes: | Review -- Export Date: 1 October 2021 -- Source: Scopus |
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