Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Genes encoding TRK are oncogenic drivers in multiple tumour types including infantile fibrosarcoma, papillary thyroid cancer and high-grade gliomas (HGG).
|
30220707 |
2018 |
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
The treatment of patients with NTRK fusion-positive cancers with a first-generation TRK inhibitor, such as larotrectinib or entrectinib, is associated with high response rates (>75%), regardless of tumour histology.
|
30333516 |
2018 |
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Recent approvals of TRK inhibitors have demonstrated the success of a tumor agnostic approach to oncogene-targeted therapy across cancers.
|
31614114 |
2019 |
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Replacement of its extracellular domain by sequences coding for the 221 amino-terminal residues of the TPM3 gene was responsible for the oncogenic NTRK1 activation in three of eight of these tumors.
|
7590742 |
1995 |
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
The same structural alterations of PTC and TRK (gene rearrangements) as well as of N-RAS (point mutation) detected in the NIH3T3 transformants, were also found in the original tumour DNAs, thus indicating that their activation was not due to transfection procedures.
|
2594368 |
1989 |
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Analysis of the residual, resected tumor identified a chromoplectic TPM3-ALK rearrangement that involved many other known oncogenes and was confirmed by rtPCR.
|
27742657 |
2016 |
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
After targeted RNA-sequencing, dual FISH fusion and array-CGH analysis, 7 of 13 tumors exhibited NTRK rearrangements (6 TPM3-NTRK1 and 1 EML4-NTRK3) and 3 a COL1A1-PDGFB fusion; in the other 3 neoplasms, all of which were positive with S100 (2 diffuse, 1 focal), we identified no rearrangement.
|
30877273 |
2019 |
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Merestinib blocks tumor growth of both wild-type and mutant G667C <i>TPM3-NTRK1</i> expressing NIH-3T3 cell-derived tumors.
|
29568395 |
2018 |
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Reciprocal NTRK1/TPM3 transcripts were found in 4 of 5 tumors with TPM3/NTRK1 re-arrangement, indicating an intra-chromosomal balanced reciprocal inversion.
|
10074915 |
1999 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
This approach led to rapid tumor responses and extended the overall duration of disease control achieved with TRK inhibition in both patients.<b>Significance:</b> LOXO-195 abrogated resistance in TRK fusion-positive cancers that acquired kinase domain mutations, a shared liability with all existing TRK TKIs.
|
28578312 |
2017 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
The TPM3-NTRK1 rearrangement is a recurring event in CRC that renders tumors sensitive to TRKA kinase inhibitors in preclinical models.
|
26563355 |
2016 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Preclinical models of LOXO-101 using TRK-fusion-bearing human-derived cancer cell lines demonstrate inhibition of the fusion oncoprotein and cellular proliferation in vitro, and tumor growth in vivo.
|
26216294 |
2015 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Hedgehog Inhibition Upregulates TRK Expression to Antagonize Tumor Suppression in Small Cell Lung Cancer Cells.
|
28870922 |
2017 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
In patients with progressive disease, we routinely send tumor tissue for next generation sequencing (NGS) to assess for the presence of actionable genomic alterations such as HER2, BRAF, and TRK fusions and offer them the option of enrollment on clinical trials with agents targeting those or other identified alterations.
|
29752549 |
2018 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
A recent "basket" study of larotrectinib, a TRK inhibitor, has demonstrated significant efficacy in TRK fusion-positive tumors of all types from infants to the elderly.
|
29880008 |
2018 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Dr. George also discussed updated data for sorafenib in the treatment of desmoid tumors, as well as the importance of larotrectinib in TRK fusion-positive tumors.
|
31117040 |
2019 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
In the context of astrocytomas, Trk receptors (TrkA, TrkB, TrkC) expression may promote tumor growth independently of grade.
|
17971243 |
2007 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Both the anti-PD-1 mAbs and the TRK-targeting therapies share some basic features: (a) biomarker-based, well-defined rare patient population; (b) exceptionally high clinical efficacy, e.g., near 40% overall response rate (ORR) for pembrolizumab across 15 tumor types with MSI-H/dMMR and 75% ORR for larotrectinib across more than 12 tumor types with NTRK-fusion proteins; (c) durable responses lasting at least 6 months with complete responses observed; and (d) parallel development in adult and pediatric populations.
|
29764494 |
2018 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Immunohistochemical staining for Trk receptors were performed using a tissue microarray containing 107 tumor samples of gastroenteropancreatic NETs.
|
29563190 |
2018 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
The only pan-TRK negative case was a core biopsy with limited tumor.
|
31498178 |
2019 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
The tumor's initial pseudoprogression may represent a unique response pattern for TRK-targeted therapies.
|
29118225 |
2017 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
The TRK inhibitor larotrectinib was well tolerated in paediatric patients and showed encouraging antitumour activity in all patients with TRK fusion-positive tumours.
|
29606586 |
2018 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Inflammatory myofibroblastic tumor with ALK/TPM3 fusion presenting as ileocolic intussusception: an unusual presentation of an unusual neoplasm.
|
16360423 |
2006 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
We provide recommendations for screening pediatric tumors for the presence of TRK fusions, including the use of immunohistochemistry or fluorescence in situ hybridization for patients with tumors likely to harbor TRK fusions.
|
30592640 |
2019 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Here, through an evaluation for TRK fusions across more than 7,000 patients with hematologic malignancies, we identified TRK fusions in acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), histiocytosis, multiple myeloma, and dendritic cell neoplasms.
|
29920189 |
2018 |