NTRK is emerging as an actionable biomarker and oncogenic driver across a wide range of tumour types1–9
NTRK fusions have been identified in at least
25 tumour types in adult and paediatric patients, including:1–9
Central nervous system cancers
- High-grade glioma (adult and paediatric)
Head and neck cancers
- Head and neck cancer
- Mammary analogue secretory carcinoma
- Papillary thyroid cancer (paediatric)
- Thyroid cancer
- Lung cancer
- Infantile fibrosarcoma (paediatric)
- Breast cancer
- Secretory breast carcinoma (adult and paediatric)
- Acute lymphoblastic leukaemia
- Acute myeloid leukaemia
- Multiple myeloma
- Dendritic cell neoplasms
- Gastrointestinal stromal tumour
- Pancreatic cancer
- Colorectal cancer
- Renal cell carcinoma
- Cellular and mixed congenital mesoblastic nephroma (paediatric)
- Spitzoid tumours
This figure is correct as of September 2019.
NTRK fusion+ cancer currently has no known defining clinical or pathological features. Only high-quality molecular testing such as next-generation sequencing (NGS) can confirm its presence1
It is important to ensure that the diagnostic test covers NTRK 1, 2, 3 fusion genes and is validated with appropriate reference standards.
Figure adapted from Marchio C. et al , 2019.
High quality molecular testing is needed to uncover NTRK fusion+ cancer1,11,12
TRKs plays an important role in healthy tissue
- The NTRK (neurotrophic tropomyosin receptor kinase) receptor family is encoded by the three NTRK genes that code for three proteins1
- In healthy tissue, the NTRK pathway is involved in the development and functioning of the nervous system as well as cell survival3,13
NTRK gene fusions create oncogenic proteins3
- Each of the three NTRK genes can combine with multiple fusion partners to create oncogenic proteins1–3,14
- So far, 25 distinct fusions have been identified1
The oncogenic proteins drive cancer through aberrant signalling1,3–6
- The oncogenic chimera proteins activate a signalling cascade implicated in cell proliferation, survival and angiogenesis1,3–6
ESMO, European Society for Medical Oncology; FISH, DNA fluorescence in situ hybridisation; IHC, immunohistochemistry; NGS, next-generation sequencing; RT-PCR, reverse-transcriptase polymerase chain reaction.
Vaishnavi A, Le AT, Doebele RC. Cancer Discov 2015;5:25–34.
Lange AM, Lo HW. Cancers (Basel) 2018;10.
Amatu A, Sartore-Bianchi A, Siena S. ESMO Open 2016;1:e000023.
Khotskaya YB, et al. Pharmacol Ther 2017;173:58–66.
de Lartigue J. TRK inhibitors advance rapidly in “tumor-agnostic” paradigm. OncologyLive 2017;18. Available at: https://www.onclive.com/publications/oncology-live/2017/vol-18-no-15/trk-inhibitors-advance-rapidly-in-tumoragnostic-paradigm (Accessed July 2020).
Robbins HL, Hague A. Front Endocrinol (Lausanne) 2016;6:1–22.
Dupain C, et al. Mol Ther Nucleic Acids 2017;6:315–326.
Kummar S, Lassen UN. Target Oncol 2018;13:545–556.
Cocco E, Scaltriti M, Drilon A. Nat Rev Clin Oncol 2018;15:731–747.
Marchio C. et al. Ann Oncol 2019;30:1417–1427.
Murphy DA, et al. Appl Immunohisochem Mol Morphol 2017;25:513–523.
Rogers TM, et al. Sci Rep 2017;7:1–8.
Chong CR, et al. Clin Cancer Res 2017;23:204–213.
Stransky N, et al. Nat Commun 2014;5:4846.