How TRK fusion drives cancer

How NTRK genes code for TRK proteins

TRK in normal, healthy tissue

  • The TRK (tropomyosin receptor kinase) receptor family is encoded by the 3 NTRK genes that code for 3 proteins 1
  • In healthy tissue, the TRK pathway is involved in the development and functioning of the nervous system as well as cell survival 3,5
How NTRK gene fusions code for TRK fusion proteins

NTRK gene fusions create oncogenic proteins 3

  • The oncogenic chimera protein activates a signaling cascade implicated in cell proliferation, survival, and angiogenesis 1,3
  • TRK fusions may be mutually exclusive to other oncogenic drivers 1-4
  • Each of the 3 NTRK genes can combine with multiple fusion partners—25 distinct fusions have been identified so far 1-4
     
How TRK fusion proteins drive tumor cell proliferation, survival, metastasis, and tumor-induced angiogenesis

TRK fusions drive cancer through aberrant signaling 1,3,6-8
 

Comprehensive molecular profiling is needed to identify oncogenic TRK fusions. 1,9,10

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AKT=v-akt murine thymoma viral oncogene homologue; DAG=diacyl-glycerol; ERK=extracellular signal-regulated kinase; MEK=mitogen-activated protein kinase; mTOR=mammalian target of rapamycin; NTRK=neurotrophic tyrosine receptor kinase; PI3K=phosphatidylinositol-4, 5-bisphosphate 3-kinase; PKC=protein kinase C; PLCy=phospholipase C gamma; RAF=rapidly accelerated fibrosarcoma kinase; Ras=rat sarcoma kinase; TRK=tropomyosin receptor kinase.