Tropomyosin receptor kinase (TRK) biology and the role of NTRK …
In this review, we discuss the normal function and physiology of TRK receptors, the biology behind NTRK gene fusions, the mechanisms by which NTRK gene fusions become oncogenic drivers in cancer, and the incidence and prevalence of NTRK gene fusions in a variety of cancers.
NTRK insights: best practices for pathologists | Modern …
2021年9月16日 · Since the discovery of an oncogenic tropomyosin-receptor kinase (TRK) fusion protein in the early 1980s, our understanding of neurotrophic tropomyosin-receptor kinase (NTRK) fusions, their unique...
NTRK fusion-positive cancers and TRK inhibitor therapy
NTRK gene fusions involving either NTRK1, NTRK2, or NTRK3 (encoding the neurotrophin receptors TRKA, TRKB, and TRKC, respectively) are oncogenic drivers of various adult and paediatric tumour types. These fusions can be detected in the clinic using a variety of methods, including tumour DNA and RNA sequencing and plasma cell-free DNA profiling.
NTRK insights: best practices for pathologists - PMC
The most common oncogenic NTRK molecular aberrations are gene fusions that result in constitutive activation of TRK signaling. Intrachromosomal or interchromosomal gene rearrangements result in the 3′ region of the NTRK gene joined with the 5′ end of a fusion partner gene (Fig. 1 ) 2 .
Phase separation underlies signaling activation of oncogenic NTRK ...
In this work, we report the condensate dysregulation mechanisms of NTRK fusion proteins in oncogenic signaling. Since kinase-targeted therapies of NTRK have inevitably led to resistant mutagenesis, targeting N-terminal fusion partners-mediated pathogenic condensates could be a promising strategy for drug development.
Revisiting NTRKs as an emerging oncogene in hematological
2019年9月24日 · NTRK fusions are dominant oncogenic drivers found in rare solid tumors. These fusions have also been identified in more common cancers, such as lung and colorectal carcinomas, albeit at low...
ERK signaling promotes resistance to TRK kinase inhibition in NTRK ...
2024年10月22日 · In summary, our results suggest that NTRK gene fusions are strong oncogenic drivers and the likely tumor-initiating events in pediatric-type NTRK fusion-positive gliomas. Tyrosine kinase inhibition is able to significantly extend survival; however, it ultimately failed to completely eliminate tumors, eventually resulting in tumor recurrence.
NTRK fusion-positive cancers and TRK inhibitor therapy
2018年10月17日 · NTRK fusions are clinically actionable: first-generation TRK tyrosine kinase inhibitors (larotrectinib or entrectinib) result in histology-agnostic responses in both adult and paediatric patients...
NTRK insights: best practices for pathologists - ScienceDirect
2022年3月1日 · Since the discovery of an oncogenic tropomyosin-receptor kinase (TRK) fusion protein in the early 1980s, our understanding of neurotrophic tropomyosin-receptor kinase (NTRK) fusions, their unique patterns of frequency in different tumor types, and methods to detect them have grown in scope and depth. Identification of these molecular ...
Oncogenic fusions: Targeting NTRK - ScienceDirect
2024年2月1日 · TRK fulfills its function primarily through the Ras/MAPK pathway and the PI3K/Akt pathway. Upon binding to neurotrophin, TRK autophosphorylates and recruits signaling molecules that play a role in both the differentiation and survival of neurons.