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Recent developments in targeting NTRK fusions for cancer therapeutics

Apr 27, 2018 3:24:21 PM No Comments

The NTRK Gene Family

Since the mid-80s, evidence has shown that gene fusions are implicated in cancer. With advances in Next Generation Sequencing (NGS) technology, the impact of gene fusions on driving cancers and how they act as potential therapeutic targets is quickly being revealed.

Currently, there is active clinical and commercial interest around the NTRK gene family as actionable drug targets in a broad range of cancers:

  • Drug companies are making progress to develop therapies that target and treat these fusions
  • NGS technology manufacturers are providing new assays for fusion detection and eligible patient identification
  • Reference standard suppliers are launching new material with characterised fusions to support advances in NGS

Larotrectinib

On 21st Feb 2018 Loxo Oncology and Bayer AG announced clinical trial results for Larotrectinib in the treatment of NTRK gene fusions1. The trial has reported striking and durable efficacy with minimal side effects2. Based on these promising results, Loxo Oncology submitted a New Drug Application to the FDA, which is expected to be complete in 2018.

This pending approval of a new targeted drug to treat NTRK fusions opens up a flurry of activity to include NTRK fusion testing in the approved repertoire offered by clinical diagnostic labs worldwide. Many of NGS assay developers now include RNA fusions in their updated NGS gene panels, such as:

  • FoundationOne - developed by Foundation Medicine
  • Oncomine™ Focus - developed by ThermoFisher Scienctific
  • TruSight Tumor 170 – developed by Illumina

Interestingly, on the 10th of April 2018 Illumunia and Loxo Oncology announced plans to develop a pan-cancer companion diagnostic to identify patients with NTRK and RET fusions who would be eligible for treatment with Larotrectinib and LOXO-292 (another new drug in clinical trials for the treatment of RET fusions)3.

This new companion diagnostic, along with other newly released cutting-edge RNA fusion NGS assays will need thorough validation with appropriate RNA fusion reference standards to ensure correct primer design, accuracy and sensitivity before being rolled out for use in clinical patient testing.

Horizon’s cell line-derived 5-Fusion Multiplex (Positive Control) and 5-Fusion Multiplex (Negative Control) RNA Reference Standard Set is compatible with all RNA Fusion assays tested to date, including TruSight Tumor 170 and Oncomine Focus.

These FFPE RNA Reference Standards enable labs to easily and reliably validate their new RNA fusion assays for the detection of fusions in the key actionable genes ALK, RET, ROS-1, NTRK1 and NTRK3.

 

See our RNA Fusion Reference Standards

References

#Oncology Panels, #NGS, #Reference Standards, #RNA, #RNA fusions

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