Herein we describe a patient with secretory carcinoma showing transdifferentiation into metaplastic carcinoma (spindle cell and squamous cell carcinoma) at the metastatic site following treatment. Identification of these morphologic shifts is crucial for accurate classification and identification of potential resistant mechanisms.

6 days ago

Journal • Metastases

NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6) • NTRK (Neurotrophic receptor tyrosine kinase)

NTRK3 fusion

NTRK-rearranged spindle cell tumor with SPECC1L-NTRK3 fusion in the thoracic spine: a case report. (PubMed, J Cancer Res Clin Oncol)

Following 1 month of entrectinib treatment, the patient experienced considerable tumor shrinkage and symptomatic improvement. For bone-derived NTRK-rearranged spindle cell sarcomas, entrectinib shows promising therapeutic efficacy and should be considered a preferred treatment option.

7 days ago

Journal

NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase) • SPECC1L (Sperm Antigen With Calponin Homology And Coiled-Coil Domains 1 Like)

NTRK3 fusion

Rozlytrek (entrectinib)

12d

Soft tissue tumor with BRAF and NRAS mutations sharing features with NTRK-rearranged spindle cell neoplasm: A case report expanding the spectrum of spindle cell tumor with kinase gene alterations. (PubMed, Pathol Int)

Since BRAF activation occurs in BRAF fusion gene tumors and BRAF mutations, they could share a similar mechanism in tumorigenesis. This case suggests the further expansion of kinase-related spindle cell tumors.

12 days ago

Journal

BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • CD34 (CD34 molecule) • NTRK (Neurotrophic receptor tyrosine kinase)

BRAF V600E • BRAF mutation • NRAS mutation • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • NRAS Q61K • NRAS Q61 • BRAF fusion • NRAS mutation + BRAF mutation

13d

Clinicopathologic and Molecular Analysis of 15 Pediatric and Young Adult Patients with High-Grade Non-anaplastic Thyroid Carcinoma. (PubMed, Endocr Pathol)

In this limited case series, two patients were dead at the last follow-up. Whether these findings are consistent within this patient population remains to be addressed as more patient series are published.

13 days ago

Journal

BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • SQSTM1 (Sequestosome 1) • DICER1 (Dicer 1 Ribonuclease III) • NTRK (Neurotrophic receptor tyrosine kinase)

BRAF V600E • BRAF V600 • NTRK3 fusion

22d

DB-1311-O-1001: A Study of DB-1311 in Advanced/Metastatic Solid Tumors (clinicaltrials.gov)

P1/2, N=450, Recruiting, DualityBio Inc. | N=280 --> 450 | Trial completion date: Apr 2025 --> Sep 2026 | Trial primary completion date: Apr 2025 --> Sep 2026

22 days ago

Enrollment change • Trial completion date • Trial primary completion date • Metastases

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • CD276 (CD276 Molecule)

BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • ALK rearrangement • MET exon 14 mutation • ROS1 rearrangement • MET mutation • RET rearrangement • KRAS G12 • NTRK1 mutation

BNT324

23d

Case report: STRN3-NTRK3 fusion in uterine sarcoma with spleen metastasis: a new variant in the spectrum of NTRK-rearranged tumors. (PubMed, Front Med (Lausanne))

The fusion involved STRN3 (exon-3) and NTRK3 (exon-14) genes and was identified through next-generation sequencing analysis. Recognizing this specific molecular rearrangement is crucial, as it not only enables targeted therapy but also holds diagnostic significance in specific clinical scenarios.

23 days ago

Journal

NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK (Neurotrophic receptor tyrosine kinase)

NTRK3 fusion

29d

ADVL1823: Larotrectinib in Treating Patients With Previously Untreated TRK Fusion Solid Tumors and TRK Fusion Relapsed Acute Leukemia (clinicaltrials.gov)

P2, N=31, Active, not recruiting, Children's Oncology Group | N=70 --> 31

29 days ago

Enrollment change

NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • ETV6 (ETS Variant Transcription Factor 6)

NTRK1 fusion • NTRK3 fusion • NTRK2 fusion

Vitrakvi (larotrectinib)

Re-verification and Report Ruling Revision of NTRK Fusion Results of Idylla GeneFusion Assay after Manufacturer Algorithm Update (AMP 2024)

Our standard operating procedure (SOP) was updated to perform orthogonal confirmation testing for stand-alone equivocal NTRK1/2 and equivocal NTRK3 (5' failure), but to ignore equivocal NTRK3 (5' intact) and report as NTRK2/3 indeterminate. Re-verification showed no change to ALK, ROS1, RET, MET ex14, and NTRK1 results. Sensitivity of NTRK2 detection was significantly increased (80% after orthogonal testing).

1 month ago

ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase)

NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • MET exon 14 mutation • ALK fusion • ROS1 fusion • NTRK fusion

Idylla™ GeneFusion Assay

Frequency of FDA-Approved Companion Diagnostic Biomarkers in Solid Tumors (AMP 2024)

Genomic profiling yields clinically actionable information for approved therapies and evidence of resistance, and it may uncover rational therapeutic opportunities regardless of tumor type.

1 month ago

Tumor mutational burden • Companion diagnostic • BRCA Biomarker • MSi-H Biomarker • BRCA Companion diagnostic • MSi-H Companion diagnostic

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • RET (Ret Proto-Oncogene) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)

BRAF V600E • KRAS mutation • BRCA2 mutation • TMB-H • MSI-H/dMMR • KRAS G12C • HER-2 negative • PIK3CA mutation • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • RET fusion • ROS1 fusion • KRAS G12 • KRAS exon 2 mutation • ALK-ROS1 fusion

OncoExTra™ test

Genomic Landscape of Fusions in Solid Tumors Detected by DNA and RNA Comprehensive Genomic Profiling at a Large Community Health System (AMP 2024)

The routine use of RNA-based CGP analysis allows for the comprehensive detection of oncogenic fusions in patients with cancer. The diversity of tumor types in which actionable fusions were detected supports the broader utilization of CGP to potentially increase targeted therapy usage and improve outcomes across cancer subtypes.

1 month ago

Tumor mutational burden

ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • RET (Ret Proto-Oncogene) • PTEN (Phosphatase and tensin homolog) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase)

TMB-H • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • RET fusion • PTEN mutation • ALK fusion

TruSight Oncology 500 Assay

Actionable Structural Variant Detection via RNA-NGS and DNA-NGS in Patients With Advanced Non-Small Cell Lung Cancer. (PubMed, JAMA Netw Open)

Emerging structural variants (eSVs) were found to have a combined prevalence to be 0.7%, with only 47.5% of eSVs detected by DNA-NGS. In this cohort study, the detection of structural variants via concurrent RNA-NGS and DNA-NGS was higher across multiple NCCN-guideline recommended biomarkers compared with DNA-NGS alone, suggesting that RNA-NGS should be routinely implemented in the care of patients with advanced NSCLC.

1 month ago

Retrospective data • Journal • Next-generation sequencing • Metastases

ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)

NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • MET exon 14 mutation • ROS1 fusion

2ms

ADVL1823: Larotrectinib in Treating Patients With Previously Untreated TRK Fusion Solid Tumors and TRK Fusion Relapsed Acute Leukemia (clinicaltrials.gov)

P2, N=70, Active, not recruiting, Children's Oncology Group | Trial completion date: Sep 2024 --> Sep 2025

2 months ago

Trial completion date

NTRK1 fusion • NTRK3 fusion • NTRK2 fusion

Vitrakvi (larotrectinib)

2ms

ON-TRK: Study to Learn More About the Safety and Effectiveness of the Drug VITRAKVI During Routine Use in Patients With TRK Fusion Cancer Which is Locally Advanced or Spread From the Place Where it Started to Other Places in the Body (clinicaltrials.gov)

P=N/A, N=150, Recruiting, Bayer | N=300 --> 150

2 months ago

Enrollment change • Metastases

NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • NTRK fusion

Vitrakvi (larotrectinib)

2ms

Larotrectinib to Enhance RAI Avidity in Differentiated Thyroid Cancer (clinicaltrials.gov)

P2, N=13, Recruiting, Children's Hospital of Philadelphia | Trial primary completion date: Oct 2024 --> Oct 2026

2 months ago

Trial primary completion date

NTRK1 fusion • NTRK3 fusion • NTRK2 fusion

Vitrakvi (larotrectinib)

2ms

Comprehensive Genomic Assessment of Advanced-Stage GI Stromal Tumors Using the Japanese National Center for Cancer Genomics and Advanced Therapeutics Database. (PubMed, JCO Precis Oncol)

This study highlights the genomic landscape of advanced GISTs and the important role of CGP in identifying rational molecular-targeted therapeutic options.

2 months ago

Retrospective data • Journal • Tumor mutational burden • PD(L)-1 Biomarker • Stroma • Metastases

HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • STK11 (Serine/threonine kinase 11) • HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • ETV6 (ETS Variant Transcription Factor 6) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • NTRK (Neurotrophic receptor tyrosine kinase) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)

TMB-H • NTRK3 fusion • HRD • ETV6-NTRK3 fusion • PDGFRA mutation • PDGFR wild-type

Keytruda (pembrolizumab)

2ms

Do not Judge a book by its Cover: A Secretory Carcinoma Arising from a Salivary Gland Heterotopia in Laterocervical lymph-node. (PubMed, Head Neck Pathol)

Tumours arising on HSGT, share histological similarities with those affecting orthotopic salivary glands. This unique case expands the understanding of SC occurrences on HSGT.

2 months ago

Journal

NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6)

NTRK3 fusion • ETV6-NTRK3 fusion

2ms

Crizotinib (Xalkori) Expanded Access Protocol for the Treatment of Adult or Pediatric Patients (clinicaltrialsregister.eu)

P4, N=14, Pfizer, Inc

2 months ago

New P4 trial

ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6)

NTRK3 fusion • ALK mutation • ETV6-NTRK3 fusion • ALK translocation

Xalkori (crizotinib)

2ms

Analysis of actionable gene fusions in a large cohort of Chinese patients with colorectal cancer. (PubMed, Gastroenterol Rep (Oxf))

Actionable gene fusions are more prevalent in MSI-H, RAS/BRAF wildtype, or RNF43-mutated CRC, as well as in colon cancer. Mapping of these molecular markers can markedly increase the fusion detection rate, which can help clinicians select candidates for fusion testing and targeted therapy.

2 months ago

Journal • MSi-H Biomarker

BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • RNF43 (Ring Finger Protein 43) • NTRK (Neurotrophic receptor tyrosine kinase)

MSI-H/dMMR • BRAF mutation • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • BRAF wild-type • RAS mutation • RNF43 mutation • NTRK fusion

2ms

S100 and CD34 positive spindle cell tumors of the uterine cervix with EGFR mutation: a hitherto unrecognized neoplasm phenotypically and epigenetically overlapping with "NTRK-rearranged spindle cell neoplasms" of the uterus. (PubMed, Virchows Arch)

The patient in case 2 had no other known tumors at the time of diagnosis, but no follow-up is available. We believe the reported cases represent a hitherto unrecognized variant of "NTRK-rearranged spindle cell neoplasms" of the uterine cervix with novel EGFR mutations.

2 months ago

Journal

EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • RET (Ret Proto-Oncogene) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • TNFRSF8 (TNF Receptor Superfamily Member 8) • CD34 (CD34 molecule) • SOX10 (SRY-Box 10) • NTRK (Neurotrophic receptor tyrosine kinase)

EGFR mutation • BRAF mutation • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • RET fusion • TNFRSF8 expression • EGFR exon 20 mutation • CD34 positive

3ms

ERK signaling promotes resistance to TRK kinase inhibition in NTRK fusion-driven glioma mouse models. (PubMed, Cell Rep)

Finally, we show that ERK activation promotes resistance to TRK kinase inhibition and identify MEK inhibition as a potential combination therapy. These models will be invaluable tools to study therapy resistance of NTRK fusion tumors.

3 months ago

Preclinical • Journal

NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • NTRK fusion

Mekinist (trametinib) • Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • Augtyro (repotrectinib)

3ms

DNA and RNA Comprehensive Genomic Profiling are Complementary for Detection of Clinically Relevant Fusions in Papillary Thyroid Carcinoma (ATA 2024)

As demonstrated in our PTC cohort, DNA CGP and RNA CGP may be complementary for fusion detection in certain tumor types. RNA CGP complements DNA CGP by detecting fusions that cannot be efficiently baited on DNA CGP, while DNA CGP may complement RNA CGP by detecting fusions in poor quality (e.g., old archival) samples when RNA sequencing may not be not technically feasible. Clinically relevant fusions detected in this retrospectively profiled PTC cohort included therapeutically targetable fusion events (e.g., RET, NTRK, ALK) and a PAX8::PPARG fusion, which is suggestive of a follicular variant PTC.

3 months ago

Clinical • Late-breaking abstract

BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • EML4 (EMAP Like 4) • CCDC6 (Coiled-Coil Domain Containing 6) • ETV6 (ETS Variant Transcription Factor 6) • TPM3 (Tropomyosin 3) • NTRK (Neurotrophic receptor tyrosine kinase) • PPARG (Peroxisome Proliferator Activated Receptor Gamma) • RBPMS (RNA-binding protein with multiple splicing) • PAX8 (Paired box 8)

NTRK3 fusion • RET fusion • ALK fusion

FoundationOne® CDx • FoundationOne®RNA

3ms

Epithelioid Fibrous Histiocytoma Is on a Continuum With Superficial ALK-rearranged Myxoid Spindle Cell Neoplasm: A Clinicopathologic Series of 35 Cases Including Alternate RET and NTRK3 Fusions. (PubMed, Am J Surg Pathol)

SAMS is on a morphologic and molecular genetic spectrum with EFH, with a similar body site distribution, frequent clinical presentation as an exophytic skin tumor, and invariably benign outcomes; we conclude that SAMS should be considered a histologic variant of EFH. Some morphologically typical examples harbor alternate RET and NTRK3 fusions, such that SAMS is not an appropriate designation for this morphologic class; instead, to highlight the clinicopathologic similarities to EFH, we propose the diagnostic term "myxoid spindle cell variant of epithelioid fibrous histiocytoma."

3 months ago

Journal

ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • EML4 (EMAP Like 4) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CD34 (CD34 molecule) • NCOA4 (Nuclear Receptor Coactivator 4) • DCTN1 (Dynactin Subunit 1) • SQSTM1 (Sequestosome 1) • MPRIP (Myosin Phosphatase Rho Interacting Protein) • SPECC1L (Sperm Antigen With Calponin Homology And Coiled-Coil Domains 1 Like) • PLEKHH2 (Pleckstrin Homology, MyTH4 And FERM Domain Containing H2) • PRKAR1A (Protein Kinase CAMP-Dependent Type I Regulatory Subunit Alpha)

NTRK3 fusion • RET fusion • ALK rearrangement • ALK fusion • CDKN2A deletion • NCOA4-RET fusion

3ms

Secretory Carcinoma of the Thyroid: A Case Report and Update of Literature. (PubMed, Head Neck Pathol)

Among documented cases of thyroid SC, prognostic factors established for salivary SC have shown broad distributions, including a mitotic activity ranging from < 1 to 10 per 10 high-power fields and variable presence of necrosis, awaiting additional case experience to better elucidate their relevance in thyroid SC. We hereby present a 61-year-old female patient with widely metastatic thyroid SC treated with larotrectinib and provide an updated review of the literature on the molecular pathogenesis and clinicopathologic characteristics of this rare entity.

3 months ago

Review • Journal

NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6) • PAX8 (Paired box 8)

NTRK3 fusion

Vitrakvi (larotrectinib)

3ms

AB055. Infantile high-grade glioma (IHG)-a case series of Hong Kong experience. (PubMed, Chin Clin Oncol)

Infantile high-grade glioma should be regarded as a unique tumor entity and a multidisciplinary approach is paramount in improving survival for this group of patients.

3 months ago

Retrospective data • Journal

ALK (Anaplastic lymphoma kinase) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6) • NTRK (Neurotrophic receptor tyrosine kinase) • HMBOX1 (Homeobox Containing 1)

NTRK1 fusion • NTRK3 fusion • ALK fusion • ETV6-NTRK3 fusion • ROS1 fusion • ALK-ROS1 fusion • TPR-NTRK1 fusion • NTRK fusion

3ms

Secretory Carcinoma of the Breast: Radiologic-Pathologic Correlation. (PubMed, J Breast Imaging)

Metastases beyond the ipsilateral axillary lymph nodes are rare, with the most common sites involving the lung and liver. Except for the potential addition of targeted drug therapy for NTRK fusion-positive tumors, the treatment approach is otherwise similar to invasive breast carcinomas of similar receptor status.

3 months ago

Review • Journal

NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6) • NTRK (Neurotrophic receptor tyrosine kinase)

NTRK3 fusion • NTRK positive • NTRK fusion

3ms

BPI-28592 as a novel second generation inhibitor for NTRK fusion tumors. (PubMed, NPJ Precis Oncol)

Clinically, BPI-28592 achieved a complete response in a patient with malignant melanoma carrying an AP3S2-NTRK3 fusion (Clinicaltrials. gov identifier: NCT05302843).

3 months ago

Journal

NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase)

NTRK3 fusion • NTRK fusion

3ms

The oncogenic fusion protein EML4-NTRK3 requires three salt bridges for stability and biological activity. (PubMed, Heliyon)

We also demonstrate that EML4-NTRK3 is localized in the cytoplasm and fails to associate with microtubules. These data suggest potential therapeutic strategies for Infantile Fibrosarcoma cases bearing EML4-NTRK3 fusion through inhibition of salt bridge interactions and disruption of multimerization.

3 months ago

Journal

NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • EML4 (EMAP Like 4) • NTRK (Neurotrophic receptor tyrosine kinase)

NTRK3 fusion • EML4-NTRK3 fusion • NTRK3 translocation

3ms

Pediatric Fibromatosis Lacks the Internal Tandem Duplication of EGFR Seen in Congenital Mesoblastic Nephroma. (PubMed, Genes Chromosomes Cancer)

The soft tissue tumors with EGFR ITD are not a morphologic match for the low-grade histology of classical CMN. Whether they have a similar favorable biology or behave more like fibrosarcoma with an ETV6::NTRK3 fusion or an alternative fusion involving other kinases remains to be determined.

3 months ago

Journal

EGFR (Epidermal growth factor receptor) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6)

NTRK3 fusion • EGFR positive

5ms

Concurrent DNA and RNA NGS Testing to Characterize Rare Fusions in Advanced NSCLC Patients (IASLC-WCLC 2024)

Importantly, co-occurrence of rare fusions and EGFR classical activating mutations in patients pre-treated with anti-EGFR therapy suggests a potential resistance mechanism and consideration of upfront, dual mutation, targeted treatment to improve outcomes. Further clinical studies are needed to validate the best treatment options for these patients with rare fusions.

5 months ago

Clinical • Next-generation sequencing • Metastases

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NRG1 (Neuregulin 1)

BRAF V600E • KRAS G12C • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • EGFR exon 19 deletion • EGFR T790M • MET exon 14 mutation • ALK fusion • ROS1 fusion • NRG1 fusion • KRAS G12 • BRAF fusion • EGFR fusion • KRAS deletion

Tempus xT Assay

5ms

Comprehensive genomic profiling provides patients access to novel matched therapies in a diverse real-world cohort of advanced lung cancer patients (ESMO 2024)

In a real-world, retrospective analysis of a cohort of advanced NSCLC patients, most oncologists utilized CGP to identify and treat patients with guideline-recommended variant matched targeted therapy, with adherence rates varying by variant. Importantly, even patients that received CGP results prior to FDA approval of novel therapies, received matched therapy once they were included in guidelines.

5 months ago

Real-world evidence • Clinical • Real-world • Metastases

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)

BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • EGFR exon 19 deletion • RET fusion • ALK fusion • RET mutation • ROS1 fusion • MET mutation • KRAS G12 • NTRK1 mutation • ALK-ROS1 fusion • NTRK3 mutation

Tempus xT Assay

7ms

NTRK3-Rearranged Prostatic Acinar Adenocarcinoma: Report of a Patient and Review of the Literature. (PubMed, Int J Surg Pathol)

This may prove to be an additional therapeutic option for patients with aggressive prostatic carcinomas refractory to initial therapy. We report a case of an aggressive castrate-resistant prostatic adenocarcinoma with a BMP6::NTRK3 gene fusion.

7 months ago

Review • Journal

NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK (Neurotrophic receptor tyrosine kinase) • BMP6 (Bone Morphogenetic Protein 6)

NTRK3 fusion • NTRK fusion

7ms

Utility of Clinical Next Generation Sequencing Tests in KIT/PDGFRA/SDH Wild-Type Gastrointestinal Stromal Tumors. (PubMed, Cancers (Basel))

Compared to KIT/PDGFRA-mutant GIST, limited benefit was observed with imatinib in triple-negative GIST. In depth molecular profiling can be helpful in identifying driver mutations and guiding therapy.

7 months ago

Journal • Next-generation sequencing • Stroma

BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • ETV6 (ETS Variant Transcription Factor 6) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • AURKA (Aurora kinase A) • SDHC (Succinate Dehydrogenase Complex Subunit C) • SDHD (Succinate Dehydrogenase Complex Subunit D) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)

TP53 mutation • BRAF V600E • BRAF V600 • NTRK3 fusion • PTEN deletion • PTEN mutation • NF1 mutation • ETV6-NTRK3 fusion • CHEK2 mutation • PDGFRA mutation • FANCA mutation • FGFR1 fusion • FANCA deletion • PDGFR wild-type

imatinib

8ms

Poorly Differentiated Thyroid Cancer: A Rare Entity (ENDO 2024)

Tyrosine kinase inhibitors i.e, sorafenib and lenvatinib, have been used in cases of progressive, recurrent, or metastatic disease not responsive to 131I therapy. PDTC accounts for 3â€“5% of all thyroid carcinomas. The 5, 10-, and 15-year survival rates of patients are 50â€“85%, 34â€“50%, and 0%, respectively. RAS gene alterations are found in 25â€“35%, BRAF mutation in 15â€“27%, TERT promoter mutation in 40% and mutant TP53 in 16â€“28% of PDTCs.

8 months ago

PD(L)-1 Biomarker • BRCA Biomarker • IO biomarker

BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • RET (Ret Proto-Oncogene) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • TERT (Telomerase Reverse Transcriptase) • NKX2-1 (NK2 Homeobox 1)

PD-L1 expression • TP53 mutation • BRAF V600E • BRCA1 mutation • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • RET fusion • RET mutation • TERT mutation • NTRK1 mutation • TERT promoter mutation • NTRK3 mutation

OmniSeq INSIGHT

sorafenib • Lenvima (lenvatinib)

8ms

Predictors of radioiodine (RAI)-avidity restoration for NTRK fusion-positive RAI resistant metastatic thyroid cancers. (PubMed, Eur Thyroid J)

Case Presentation and We report two cases with RAI-resistant lung metastases treated with larotrectinib: 83-year-old male presenting with an ETV6::NTRK3 fusion-positive tumor with the TERT promoter mutation c.-124C>T, and a 31-year-old female presenting with a TPR::NTRK1 fusion-positive tumor (and negative for TERT promoter mutation)...In contrast, the TERT-negative tumor exhibited successful I-131 reuptake with a TDS of -0.060. As observed for RAI-resistance associated with concurrent TERT and BRAF mutations, the co-occurrence of TERT mutations and NTRK fusions may also contribute to re-sensitization failure.

8 months ago

Journal • Metastases

BRAF (B-raf proto-oncogene) • RET (Ret Proto-Oncogene) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • TERT (Telomerase Reverse Transcriptase) • ETV6 (ETS Variant Transcription Factor 6) • NTRK (Neurotrophic receptor tyrosine kinase)

BRAF mutation • NTRK1 fusion • NTRK3 fusion • RET fusion • TERT mutation • TERT promoter mutation • NTRK1 positive • NTRK3 positive • BRAF mutation + TERT −124C>T • NTRK positive • RET positive • TERT 124C>T • NTRK fusion

Vitrakvi (larotrectinib)

8ms

ETV6::NTRK3 Fusion-Positive Wild-Type Gastrointestinal Stromal Tumor (GIST) with Abundant Lymphoid Infiltration (TILs and Tertiary Lymphoid Structures): A Report on a New Case with Therapeutic Implications and a Literature Review. (PubMed, Int J Mol Sci)

The follow-up CT scan revealed peritoneal nodules suggestive of peritoneal dissemination, and Entrectinib (a TRK inhibitor) was administered...The present case may offer new insights into the potential introduction of TRK inhibitors as treatments for GISTs with NTRK fusions. Additionally, the presence of abundant lymphoid infiltration in the present case may prompt further research into immunotherapy as a possible additional therapeutic option.

8 months ago

Clinical • Observational data • Retrospective data • Review • Journal • IO biomarker • Stroma

KIT (KIT proto-oncogene, receptor tyrosine kinase) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • RB1 (RB Transcriptional Corepressor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • ETV6 (ETS Variant Transcription Factor 6) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • TFG (Trafficking From ER To Golgi Regulator) • NTRK (Neurotrophic receptor tyrosine kinase) • ANO1 (Anoctamin 1)

NTRK3 fusion • RB1 mutation • PDGFRA mutation • NTRK3 positive • NTRK fusion

Rozlytrek (entrectinib)

8ms

RAF1 gene fusions are recurrent driver events in infantile fibrosarcoma-like mesenchymal tumors. (PubMed, J Pathol)

Our findings document that RAF1 gene rearrangements represent a recurrent event in ETV6::NTRK3-negative IFS/CMN and provide a rationale for the use of inhibitors directed to suppress MAPK and PI3K-AKT signaling in these cancers.

8 months ago

Journal

NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • GOLGA4 (Golgin A4) • CLIP1 (CAP-Gly Domain Containing Linker Protein 1)

NTRK3 fusion

8ms

The Molecular Landscape of Gastric Cancers for Novel Targeted Therapies from Real-World Genomic Profiling. (PubMed, Target Oncol)

Real-world datasets from clinical panel testing revealed the genomic landscape in gastric cancer by subgroup. These findings provide insights for the current therapeutic strategies and future development of treatments in gastric cancer.

8 months ago

Journal • Real-world evidence • Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker • Real-world

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • CDH1 (Cadherin 1)

BRAF V600E • TMB-H • MSI-H/dMMR • KRAS G12C • HER-2 amplification • PIK3CA mutation • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • MET amplification • MET mutation • KRAS G12

8ms

A Study to Evaluate the Efficacy and Safety of TL118 in Solid Tumors Patients (clinicaltrials.gov)

P2, N=60, Not yet recruiting, Teligene US | Initiation date: Jan 2024 --> May 2024

8 months ago

Trial initiation date

NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)

NTRK1 fusion • NTRK3 fusion • NTRK2 fusion

TL118

9ms

ADVL1823: Larotrectinib in Treating Patients With Previously Untreated TRK Fusion Solid Tumors and TRK Fusion Relapsed Acute Leukemia (clinicaltrials.gov)

P2, N=70, Active, not recruiting, Children's Oncology Group | Trial completion date: Mar 2024 --> Sep 2024 | Trial primary completion date: Mar 2024 --> Sep 2024

9 months ago

Trial completion date • Trial primary completion date

NTRK1 fusion • NTRK3 fusion • NTRK2 fusion

Vitrakvi (larotrectinib)

9ms

NAUTIKA1: A Study of Multiple Therapies in Biomarker-Selected Patients With Resectable Stages IB-III Non-Small Cell Lung Cancer (clinicaltrials.gov)

P2, N=146, Recruiting, Genentech, Inc. | N=85 --> 146

9 months ago

Enrollment change

PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)

PD-L1 expression • KRAS mutation • KRAS G12C • BRAF mutation • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • RET fusion • ALK fusion • RET mutation • ROS1 fusion • KRAS G12 • ALK-ROS1 fusion

Tecentriq (atezolizumab) • Zelboraf (vemurafenib) • Rozlytrek (entrectinib) • Alecensa (alectinib) • Cotellic (cobimetinib) • Gavreto (pralsetinib) • divarasib (RG6330)

9ms

NAUTIKA1: A Study of Multiple Therapies in Biomarker-Selected Patients With Resectable Stages IB-III Non-Small Cell Lung Cancer (clinicaltrials.gov)

P2, N=85, Recruiting, Genentech, Inc. | Trial primary completion date: Mar 2024 --> Dec 2025

9 months ago

Trial primary completion date

Tecentriq (atezolizumab) • Zelboraf (vemurafenib) • Rozlytrek (entrectinib) • Alecensa (alectinib) • Cotellic (cobimetinib) • Gavreto (pralsetinib) • divarasib (RG6330)

9ms

Clinicopathological analysis of thyroid carcinomas with the RET and NTRK fusion genes: characterization for genetic analysis. (PubMed, Virchows Arch)

This study highlights the benefits of combining morphological and immunohistochemical analyses for gene detection and posits that lymph node metastases are more suitable for genetic analysis owing to their mild calcification. Our results emphasize the importance of accurate sample processing in diagnosing and treating thyroid carcinomas.

9 months ago

Journal

BRAF (B-raf proto-oncogene) • RET (Ret Proto-Oncogene) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • RAS (Rat Sarcoma Virus) • NTRK (Neurotrophic receptor tyrosine kinase)

BRAF V600E • BRAF V600 • NTRK3 fusion • RET fusion • NTRK fusion

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