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
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
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.
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de Lartigue J. TRK inhibitors advance rapidly in “tumor-agnostic” paradigm. OncologyLive 2017;18.
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