Biological and Clinical Implications

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Oncogenic gene fusions involving the neurotrophic tyrosine receptor kinase (NTRKoccur in numerous adult and paediatric tumour types [1-4], and have thus emerged as a promising therapeutic target across several tumour histologies [1]. The estimated frequency of NTRK gene fusions varies between tumour types ranging from a prevalence of >90% in some rare cancers (secretory carcinoma of the breast and salivary glands and infantile fibrosarcoma) to <1% in more common cancer types (click here  to learn more about the epidemiology of NTRK gene fusions) [1-3]. The protein product of NTRK gene fusions (referred to as a tropomyosin receptor kinase [TRK] fusion protein) is constitutively active and results in cell growth, proliferation and survival pathway activation [1, 3, 4].

References

  1. Amatu A, Sartore-Bianchi A, Siena S. NTRK gene fusions as novel targets of cancer therapy across multiple tumour types. ESMO Open 2016; 1: e000023.
  2. Stransky N, Cerami E, Schalm S et al. The landscape of kinase fusions in cancer. Nat Commun 2014; 5: 4846.
  3. Cocco E, Scaltriti M, Drilon A. NTRK fusion-positive cancers and TRK inhibitor therapy. Nat Rev Clin Oncol 2018; 15: 731-747.
  4. Vaishnavi A, Le AT, Doebele RC. TRKing down an old oncogene in a new era of targeted therapy. Cancer Discov 2015; 5: 25-34.
Last update: 24 June 2019