About oncogenetic drivers

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)


Thyroid cancers

Papillary thyroid cancer (paediatric)

Thyroid cancer



Infantile fibrosarcoma (paediatric)

Blood cancers

Acute lymphoblastic leukaemia

Acute myeloid leukaemia


Multiple myeloma

Dendritic cell neoplasms


Genitourinary cancers

Renal cell carcinoma

Cellular and mixed congenital mesoblastic nephroma (paediatric)

Head and neck cancers

Head and neck cancer

Mammary analogue secretory carcinoma

Thoracic cancers

Lung cancer


Breast cancers

Breast cancer

Secretory breast carcinoma (adult and paediatric)


Gastrointestinal cancers

Gastrointestinal stromal tumour


Pancreatic cancer

Colorectal cancer



Skin cancers


Spitzoid tumours


These figures are 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

ESMO proposal: NTRK testing10

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

TRK fusion proteins drive cancer through aberrant signalling1,3-6

TRKs play 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 other gene partners to create oncogenic fusion proteins1–3,14
  • So far, 25 distinct fusions have been identified1

The oncogenic fusion proteins drive cancer through aberrant signalling1,3–6


  • The oncogenic fusion proteins constitutively 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.



1. Vaishnavi A, Le AT, Doebele RC. Cancer Discov 2015;5:25–34.

2. Lange AM, Lo HW. Cancers (Basel) 2018;10.

3. Amatu A, Sartore-Bianchi A, Siena S. ESMO Open 2016;1:e000023.

4. Khotskaya YB, et al. Pharmacol Ther 2017;173:58–66.

5. 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).

6. Robbins HL, Hague A. Front Endocrinol (Lausanne) 2016;6:1–22.

7. Dupain C, et al. Mol Ther Nucleic Acids 2017;6:315–326.

8. Kummar S, Lassen UN. Target Oncol 2018;13:545–556.

9. Cocco E, Scaltriti M, Drilon A. Nat Rev Clin Oncol 2018;15:731–747. 

10. Marchio C. et al. Ann Oncol 2019;30:1417–1427.

11. Murphy DA, et al. Appl Immunohisochem Mol Morphol 2017;25:513–523.

12. Rogers TM, et al. Sci Rep 2017;7:1–8.

13. Chong CR, et al. Clin Cancer Res 2017;23:204–213.

14. Stransky N, et al. Nat Commun 2014;5:4846.

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