Importance of NTRK  testing

Studies show that a significant number of patients harbour potentially targetable alterations, and that a large proportion of those patients who undergo genomic testing may benefit from being paired with an approved or investigational targeted therapy1,2

TRK fusion proteins are often a primary oncogenic driver across multiple tumour types3,4

A subset of gene fusions involves NTRK1, NTRK2, and NTRK3 3

  • NTRK gene fusions lead to TRK fusion proteins that are oncogenic drivers5
  • The presence of TRK fusion proteins has been associated with more aggressive cancer in some tumour types, highlighting an unmet medical need among TRK fusion cancer patients6,7
  • While NTRK gene fusions were one of the first oncogenes identified, they are not routinely tested for and/or included on all test platforms3,8
  • TRK fusion cancers can be detected through a number of testing methodologies; however, only sensitive and specific tests can reliably detect NTRK gene fusions3,8
  • Testing for NTRK gene fusions is essential to identify patients who harbour these genomic alterations9

NTRK=neurotrophic tyrosine receptor kinase; TRK=tropomyosin receptor kinase.

References: 1. Massard C, et al. High-throughput genomics and clinical outcome in hard-to-treat advanced cancers: results of the MOSCATO 01 trial. Cancer Discov 2017;7(6):586–95. 2. Boland GM, et al. Clinical next generation sequencing to identify actionable aberrations in a phase I program. Oncotarget 2015;6(24):20099-20110. 3. Vaishnavi A, et al. TRKing Down an Old Oncogene in a New Era of Targeted Therapy. Cancer Discov 2015;5(1):25–34. 4. Okimoto RA, et al. Tracking down response and resistance to TRK inhibitors. Cancer Discov 2016;6(1):14–16. 5. Amatu A, et al. NTRK gene fusions as novel targets of cancer therapy across multiple tumour types. ESMO Open. 2016;1:e000023. doi:10.1136/esmoopen-2015-000023 6. Lange AM, et al. Inhibiting TRK proteins in clinical cancer therapy. Cancers 2018;10(4):E105. doi:10.3390/cancers10040105. 7. Musholt TJ, et al. Prognostic significance of RET and NTRK1 rearrangements in sporadic papillary thyroid carcinoma. Surgery 2000;128(6):984-993. 8. Kumar-Sinha C, et al. Landscape of gene fusions in epithelial cancers: seq and ye shall find. Genome Med 2015;7:129. 9. Kummar S, et al. TRK Inhibition: A New Tumor-Agnostic Treatment Strategy. Target Oncol 2018;13(5):545-556.