Targeted therapies are being studied to advance treatment options for patients with actionable biomarkers – patients with gene fusions need high-quality molecular testing to realise these opportunities.1,2
Neurotrophic tropomyosin receptor kinase (NTRK) gene fusions are emerging as actionable biomarkers and oncogenic drivers across a wide range of tumour types.1–6 NTRK fusion positive cancer currently has no known defining clinical or pathological features.1–3
Only high quality molecular testing such as next-generation sequencing (NGS) can confirm NTRK fusion positive cancer.1
Knowing a patient’s biomarker profile can open up new targeted treatment options.7–9 High-quality NGS helps you see beyond the tumour origin to know exactly which mutations are driving that cancer.10
Precision medicine combines different treatment options, including traditional cancer therapies and emerging targeted therapies, with the aim of achieving the best possible outcome for the patient.11
A number of diagnostic options are available for the identification of gene fusions. However, not all are equally reliable.1,12–17
Roche is committed to pioneering progress in precision medicine.18
TRK fusion proteins have been identified in a wide range of commonly occurring tumors, such as lung cancer, thyroid cancer and sarcoma, but at low frequencies.1-7 In very rare tumors, such as infantile fibrosarcoma, secretory/juvenile breast cancer and mammary analogue secretory cancers (MASC, secretory carcinoma) of the salivary glands, TRK fusion proteins are likely to be the defining genetic feature.8-12
The Neurotrophic tropomyosin receptor kinase (NTRK) 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 survival2,3
Each of the three NTRK genes can combine with multiple fusion partners to create oncogenic proteins1–4
So far, 25 distinct fusions have been identified1
NTRK fusion positive cancer currently has no known defining clinical or pathological features. Only high-quality molecular testing can confirm its presence.1 It is important to ensure that the diagnostic test covers NTRK 1, 2, 3 fusion genes and is validated with appropriate reference standards.1
European Society for Medical Oncology (ESMO) have published recommendations outlining a strategy for NTRK gene-fusion testing. As part of this testing approach, the use of pan-TRK IHC to identify patients with solid tumors allows you to focus on those who may benefit from next-generation sequencing.
Only sensitive and specific tests can reliably detect NTRK.1–3 There are multiple molecular tests available for detecting gene fusions, but some are more specific than others.1,2,4–11
FFPE = Formalin-fixed and paraffin-embedded
NGS = Next-generation sequencing
IHC = Immunohistochemistry
FISH = Fluorescence in situ hybridisation
RT-PCR = Reverse transcriptase polymerase chain reaction