TRK fusion proteins are often
oncogenic drivers in a wide
variety of tumor types in both
adult and pediatric patients1,2

  • Research has identified NTRK gene fusions in more than 2 dozen types of common and rare solid tumors1,3-5
  • The presence of TRK proteins has been associated with more aggressive cancer in some tumor types5-7
  • Traditional approaches to the treatment of solid tumors are not designed to directly impact NTRK gene fusions or TRK proteins8

Selected tumor types in which
NTRK gene fusions
have been identified:

NTRK gene fusions identified in infantile fibrosarcoma, thyroid cancer, high-grade gliomas (pediatric), lung, colon, sarcoma, glioblastoma, head and neck squamous cell carcinoma
Infantile fibrosarcoma9-11


Thyroid cancer2,12a


High-grade gliomas


Lung cancer14,15


Colon cancer14,16






Head and neck squamous
cell carcinoma2


Frequencies reported from isolated studies that used variable methodologies to detect these genetic alterations.

aPapillary thyroid carcinoma; 25.9% incidence based on pediatric population only.

bLung adenocarcinoma that did not contain other common oncogenic alterations.

Even though it’s not a common alteration, learning that an NTRK gene fusion is the driver of a patient’s cancer would be a meaningful discovery.
—Federico Cappuzzo, MD


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References: 1. Amatu A, Sartore-Bianchi A, Siena S. ESMO Open. 2016;1(2):e000023. 2. Stransky N, Cerami E, Schalm S, Kim JL, Lengauer C. The landscape of kinase fusions in cancer. Nat Commun. 2014;5:4846. doi:10.1038/ncomms5846. 3. Vaishnavi A, Le AT, Doebele RC. Cancer Discov. 2015;5(1):25-34. 4. Okimoto RA, Bivona TG. Tracking down response and resistance to TRK inhibitors. Cancer Discov. 2016;6(1):14-16. 5. Lange AM, Lo H-W. Inhibiting TRK proteins in clinical cancer therapy. Cancers. 2018;10(4):E105. doi:10.3390/cancers10040105. 6. Musholt TJ, Musholt PB, Khaladj N, Schulz D, Scheumann GFW, Klempnauer J. Prognostic significance of RET and NTRK1 rearrangements in sporadic papillary thyroid carcinoma. Surgery. 2000;128(6):984-993. 7. Okamura K, Harada T, Wang S, et al. Expression of TrkB and BDNF is associated with poor prognosis in non-small cell lung cancer. Lung Cancer. 2012;78(1):100-106. 8. Padma VV. An overview of targeted cancer therapy. BioMedicine. 2015;5(4):1-6. doi:10.7603/s40681-015-0019-4. 9. Knezevich SR, McFadden DE, Tao W, Lim JF, Sorensen PHB. A novel ETV6-NTRK3 gene fusion in congenital fibrosarcoma. Nat Genet. 1998;18(2):184-187. 10. Church AJ, Calicchio ML, Nardi V, et al. Recurrent EML4–NTRK3 fusions in infantile fibrosarcoma and congenital mesoblastic nephroma suggest a revised testing strategy. Mod Pathol. 2018;31(3):463-473. 11. Orbach D, Brennan B, De Paoli A, et al. Conservative strategy in infantile fibrosarcoma is possible: the European paediatric Soft tissue sarcoma Study Group experience. Eur J Cancer. 2016;57:1-9. 12. Prasad ML, Vyas M, Horne MJ, et al. NTRK fusion oncogenes in pediatric papillary thyroid carcinoma in northeast United States. Eur J Cancer. 2016;122(7):1097-1107. 13. Wu G, Diaz AK, Paugh BS, et al. The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. Nat Genet. 2014;46(5):444-450. 14. Gatalica Z, Xiu J, Swensen J, Vranic S. Molecular characterization of cancers with NTRK gene fusions. Mod Pathol. 2019;32(1):147-153. 15. Vaishnavi A, Capelletti M, Le AT. Oncogenic and drug sensitive NTRK1 rearrangements in lung cancer. Nat Med. 2013;19(11):1469-1472. 16. Lee SJ, Li GG, Kim ST, et al. NTRK1 rearrangement in colorectal cancer patients: evidence for actionable target using patient-derived tumor cell line. Oncotarget. 2015;6(36):39028-39035. 17. Kim J, Lee Y, Cho H-J, et al. NTRK1 fusion in glioblastoma multiforme.PLoS One. 2014;9(3):e91940. doi:10.1371/journal.pone.0091940.