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DETECTING NTRK GENE FUSIONS

3/29/2019

The NTRK gene family encodes three receptor tyrosine kinases that have long been known to play a role in survival and differentiation of distinct cell types.

Clinical interest in these genes has increased drastically in recent years after oncogenic fusions of these genes have been found in a wide range of tumors.

Gene fusions involving NTRK1, NTRK2 or NTRK3 have been found in many solid tumor types, including a number of quite rare cancers where they occur in a high percentage of cases. As a result, the oncogenic fusion derivatives of the protein products of these genes, TrkA, TrkB and TrkC, have emerged as highly promising targets for cancer therapy.

 

A number of inhibitors of these oncogenic fusion proteins are now in different stages of preclinical and clinical development. Of several selective pan-TRK inhibitors in clinical trials, Larotrectinib is the most advanced. While not the first FDA-approved therapeutics that targets a specific genomic aberration, Larotrectinib was the first drug to be developed - from the start – to treat any cancer harboring a certain type of mutation - irrespective of tumor type and tissue location. It was granted orphan drug status in 2015 and received breakthrough designation in 2017. It was FDA approved in late 2018 for the treatment of metastatic solid tumors with NTRK gene fusions; further clinical trials are ongoing as well.

Another novel tyrosine kinase inhibitor drug in development is Entrectinib, which has also received orphan drug status and is currently in a number of phase I and phase II clinical trials. In addition to inhibiting tumors harboring fusions of the three tropomyosin kinase receptor genes NTRK1, NTRK2 and NTRK3, Entrectinib is also active against tumors harboring ROS1 and ALK receptor gene fusions. Entrectinib is expected to be FDA approved very soon.

 

NTRK gene fusions in patient tumors can be detected by a number of diagnostic test methods, the most widely used of which are next generation sequencing (NGS), and the gold standard test system for genomic aberrations, fluorescence in situ hybridization (FISH).

 

CytoTest Inc. is providing a complete range of NTRK FISH products, manufactured for research applications (RUO) or as U.S.-FDA ASR or CE-IVD reagents.

In addition to offering a wide range of FISH products, the company is also facilitating the running of NTRK1, 2 and 3 testing services. Nexome Genomics Inc will be using our probes on their FISH and NGS platforms.

 

NTRK1

https://www.cytotest.com/enn/tercshow.asp?ID=4164

NTRK2

https://www.cytotest.com/enn/tercshow.asp?ID=4311

NTRK3

https://www.cytotest.com/enn/tercshow.asp?ID=4299

https://www.cytotest.com/enn/tercshow.asp?ID=4285

 

ROS1

https://www.cytotest.com/tercshow.asp?ID=779

ALK

https://www.cytotest.com/tercshow.asp?ID=154

 
   

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