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

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

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

NTRK fusion proteins drive cancer through aberrant signalling1,3–6

NTRKs 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

Footnotes:

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 April 2019).

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. Nature Reviews Clin Oncl 2018;15:731–747. 

10

Marchio C. et al. Annals of Oncology 2019. DOI: https://doi.org/10.1093/annonc/mdz204. 

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.