Larotrectinib, a selective tropomyosin receptor kinase inhibitor for adult and pediatric tropomyosin receptor kinase fusion cancers

Future Oncology
Anna F Farago, George D Demetri

Abstract

Gene fusions involving NTRK1, NTRK2 and NTRK3 are oncogenic drivers across a wide variety of cancer types. Inhibitors of the chimeric TRKA/B/C protein kinases encoded by these fusions are now available, including larotrectinib, a potent and highly selective oral drug. Integrated data from three trials demonstrate substantial clinical activity of larotrectinib in patients with many different types of cancers harboring NTRK fusions. Larotrectinib has received accelerated approval from both the US FDA and the EMA. Resistance mutations have been observed in the kinase domains of the NTRK fusion genes and development of next-generation tropomyosin receptor kinase inhibitors designed to overcome such resistance mutations is being actively pursued in clinical trials and ongoing drug discovery efforts.

References

Nov 15, 2005·The Journal of Biological Chemistry·Juan Carlos ArévaloMoses V Chao
Sep 21, 2007·Developmental Biology·Kazuhiro KawamuraToshinobu Tanaka
Oct 18, 2013·Nature Reviews. Cancer·Alice T ShawJeffrey A Engelman
Oct 29, 2013·Nature Medicine·Aria VaishnaviRobert C Doebele
Nov 11, 2014·Nature Medicine·Zongli ZhengLong Phi Le
Dec 21, 2014·Cancer Discovery·Aria VaishnaviRobert C Doebele
May 23, 2015·Nature Reviews. Cancer·Fredrik MertensFelix Mitelman
Nov 8, 2015·Cancer Discovery·Mariangela RussoAlberto Bardelli
Feb 18, 2016·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A DrilonA L Ho
Jul 19, 2017·The American Journal of Surgical Pathology·Jaclyn F HechtmanAchim A Jungbluth
Nov 4, 2017·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Alanna J ChurchMarian H Harris
Feb 22, 2018·The New England Journal of Medicine·Alexander DrilonDavid M Hyman
Jan 10, 2019·Annals of Oncology : Official Journal of the European Society for Medical Oncology·D S HongR C Doebele
May 11, 2019·Journal of Clinical Pathology·Frédérique Penault-LlorcaAntonia R Sepulveda
Jul 4, 2019·Annals of Oncology : Official Journal of the European Society for Medical Oncology·C MarchiòJ S Reis-Filho
Aug 4, 2019·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·James P SolomonJaclyn F Hechtman
Aug 14, 2019·Nature Medicine·Emiliano CoccoMaurizio Scaltriti
Jan 29, 2020·Annals of Oncology : Official Journal of the European Society for Medical Oncology·C MarchiòJ S Reis-Filho
Jan 29, 2020·Annals of Oncology : Official Journal of the European Society for Medical Oncology·D S HongR C Doebele
Oct 1, 2018·Annals of Oncology : Official Journal of the European Society for Medical Oncology·U N LassenD S Hong

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Methods Mentioned

BETA
xenograft
xenografts
surgical resection

Clinical Trials Mentioned

NCT02122913
NCT02637687
NCT02576431
NCT03215511
NCT02568267
NCT03093116
NCT02920996

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