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Example clinical scenario

A 77-year-old man has mesothelioma and has progressed through available treatment options. Somatic (tumour) testing via a multi-target massively parallel sequencing (sometimes called next-generation sequencing) panel has revealed an NTRK rearrangement.

Impact of the genomic result

  • The NTRK genes NTRK1, NTRK2 and NTRK3 encode neurotrophin receptors TRKA, TRKB and TRKC respectively.
  • NTRK fusion genes are formed when rearrangements – such as translocations or inversions – occur between or within chromosomes in such a way that an NTRK gene is brought into contact and fuses with a partner, such as ETV6, LMNA or TPM3. This NTRK-partner gene fusion results in a fusion protein product that constitutively activates downstream signalling pathways, such as MAPK, PI3K and PKC.
  • NTRK fusion genes are oncogenic drivers of various adult and paediatric tumours.
  • NTRK fusion genes are found in about 1% of all solid tumours, but frequency varies significantly between different tumour types.
  • NTRK fusions are present in <1% of pleural mesotheliomas.
  • NTRK inhibitors are targeted therapies associated with high response rates in NTRK-fusion positive cancers, regardless of the tumour histology.

What do you need to do?

  • Patients with mesothelioma and an NTRK rearrangement who have no satisfactory treatment options are eligible for treatment with the NTRK inhibitor drugs entrectinib or larotrectinib.
  • These drugs are currently made available via the Cancer Drugs Fund.
  • Overall, data are limited for the efficacy of NTRK inhibitors in treating mesothelioma owing to the low frequency of eligible patients. However, these drugs offer a further choice of therapy in a tumour type in which options are limited.
  • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see our dedicated Knowledge Hub resource.
  • Information about patient eligibility and test indications was correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.


For clinicians


For patients

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  • Last reviewed: 27/01/2024
  • Next review due: 27/01/2025
  • Authors: Dr Ellen Copson, Dr Jemma Longley
  • Reviewers: Dr Terri McVeigh