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BIOMARKER:

NTRK1 mutation

i
Other names: NTRK1, MTC, TRK, TRKA, Neurotrophic tyrosine kinase, receptor, type 1
Entrez ID:
15d
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 3–5% of all thyroid carcinomas. The 5, 10-, and 15-year survival rates of patients are 50–85%, 34–50%, and 0%, respectively. RAS gene alterations are found in 25–35%, BRAF mutation in 15–27%, TERT promoter mutation in 40% and mutant TP53 in 16–28% of PDTCs.
BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker
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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)
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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
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OmniSeq INSIGHT
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sorafenib • Lenvima (lenvatinib)
26d
Prevalence and detection methodology for preliminary exploration of NTRK fusion in gastric cancer from a single-center retrospective cohort. (PubMed, Hum Pathol)
FISH could complement NGS detection, particularly when NTRK fusion is detected by DNA sequencing. NTRK fusion in GC may not be limited to specific subtypes.
Retrospective data • Journal
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HER-2 (Human epidermal growth factor receptor 2) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK1 fusion • LMNA-NTRK1 fusion • NTRK1 mutation • NTRK fusion
1m
An odd dancing couple. Non-small cell lung carcinoma with coexisting EGFR mutation and NTRK-1 translocation: A case report. (PubMed, Diagn Cytopathol)
Moreover, so was the case with the concomitant expression of NTRK fusions and EGFR mutations. We present a case report of a patient with concomitant EGFR mutation and NTRK1 fusion.
Journal
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • 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) • NTRK (Neurotrophic receptor tyrosine kinase)
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EGFR mutation • NTRK1 fusion • NTRK1 mutation • NTRK expression • NTRK fusion
1m
Agnostic Administration of Targeted Anticancer Drugs: Looking for a Balance between Hype and Caution. (PubMed, Int J Mol Sci)
Several agnostic drug-target matches have already been approved for clinical use, e.g., immune therapy for tumors with microsatellite instability (MSI) and/or high tumor mutation burden (TMB), NTRK1-3 and RET inhibitors for cancers carrying rearrangements in these kinases, and dabrafenib plus trametinib for BRAF V600E mutated malignancies. The existing format of data dissemination may not be optimal for agnostic cancer medicine, as conventional scientific journals are understandably biased towards the publication of positive findings and usually discourage the submission of case reports. Despite all the limitations and concerns, histology-independent drug-target matching is certainly feasible and, therefore, will be increasingly utilized in the future.
Review • Journal • Tumor mutational burden • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • 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) • HRD (Homologous Recombination Deficiency)
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PD-L1 expression • BRAF V600E • TMB-H • HER-2 overexpression • HER-2 amplification • BRAF V600 • HRD • RET mutation • ALK translocation • NTRK1 mutation • HER-2 amplification + PD-L1 expression
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Mekinist (trametinib) • Tafinlar (dabrafenib)
2ms
A recurrent NTRK1 tyrosine kinase domain mutation pair is characteristic in a subset of dedifferentiated liposarcomas. (PubMed, Eur J Cancer)
We detected (de novo/somatic) missense mutation variants in cis position of the NTRK1 gene in a subset of DDLPS indicating modifying mutations that may contribute to tumorigenesis in a subset of DDLPS. These variants beget resistance to TRK inhibitors indicating an interesting biomarker for other studies with TRK inhibitors.
Journal
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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)
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NTRK1 mutation • NTRK fusion
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Vitrakvi (larotrectinib) • selitrectinib (BAY 2731954)
4ms
Selective TrkA Inhibitor VMD-928 to Treat TrkA Overexpression Driven Solid Tumors or Lymphoma (clinicaltrials.gov)
P1, N=74, Recruiting, VM Oncology, LLC | Trial completion date: Jun 2025 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Jun 2025
Trial completion date • Trial primary completion date
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1)
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NTRK1 fusion • NTRK1 mutation • NTRK expression
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VMD-928
6ms
A Misleading Case of NTRK-Rearranged Papillary Thyroid Carcinoma. (PubMed, Oncologist)
Between August 2019 and August 2020, the patient received 2 ineffective lines of systemic therapy, including a first line of chemotherapy with cisplatin and pemetrexed, and a second line of immunotherapy with atezolizumab. After palliative partial thyroidectomy that confirmed the diagnosis of papillary thyroid carcinoma, in February 2021, the patient was enrolled in the STARTRK-2 GO40782 basket trial and received entrectinib, an oral pan-TRK inhibitor specifically targeting NTRK-rearranged tumors. After initially experiencing drug-related grade 2 anorexia, dysgeusia, and neurotoxicity and grade 3 asthenia, the dose was reduced, and an excellent and durable objective response was observed.
Journal • PD(L)-1 Biomarker • IO biomarker
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • TERT (Telomerase Reverse Transcriptase) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK1 fusion • TERT mutation • NTRK1 mutation
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cisplatin • Tecentriq (atezolizumab) • Rozlytrek (entrectinib) • pemetrexed
8ms
B Targeted Therapy Matched To Genomic Alterations (Brafv600E, Ntrk, Fgfr, Ros1, Pik3Ca, Pten) In Patients With Recurrent Idh Wildtype Glioblastoma: A Real-Life Cohort Analysis From Veneto Institute Of Oncology, Padua (Italy) (EANO 2023)
All patients received radiotherapy and temozolomide as first-line therapy...TT was dabrafenib/trametinib (9 pts), larotrectinib (2 pts), erdafitinib (4 pts), entrectinib (1 pt), alpelisib (6 pts), ipatasertib+/-atezolizumab (12 pts)... Our results confirm the activity of dabrafenib/trametinib in BRAFV600E mutant glioblastoma pts and might suggest deeper explorations in targeting ROS1 and FGFR. Further correlation among patients' outcome, molecular characteristics and TT timing are still under investigation.
Clinical • PD(L)-1 Biomarker
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • 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) • FGFR1 (Fibroblast growth factor receptor 1) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • FGFR (Fibroblast Growth Factor Receptor) • NTRK (Neurotrophic receptor tyrosine kinase)
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BRAF V600E • PIK3CA mutation • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • ROS1 fusion • FGFR1 fusion • IDH wild-type • NTRK1 mutation • PIK3CA mutation + PTEN mutation • NTRK3 mutation
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FoundationOne® CDx
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Mekinist (trametinib) • Tecentriq (atezolizumab) • Tafinlar (dabrafenib) • Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • temozolomide • Piqray (alpelisib) • Balversa (erdafitinib) • ipatasertib (RG7440)
8ms
New options and open issues in the management of unresectable stage III and in early-stage NSCLC: a report from an expert panel of Italian medical and radiation oncologists - INTERACTION GROUP. (PubMed, Crit Rev Oncol Hematol)
Treatment of stage III NSCLC has always been controversial and challenging: Multidisciplinary approach is mandatory and defining resectability is a critical issue. Chemo-radiotherapy followed by maintenance Durvalumab is now the standard of treatment. Herein, we provide a comprehensive overview of the key challenges and open questions that we are currently facing in clinical practice, in unresectable stage III and in early-stage NSCLC, identifying the knowledge gaps and the possible solutions.
Review • Journal • PD(L)-1 Biomarker • IO biomarker
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma 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)
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EGFR mutation • HER-2 mutation • RET mutation • RET rearrangement • NTRK1 mutation
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Imfinzi (durvalumab)
8ms
A Study of DB-1311 in Advanced/Metastatic Solid Tumors (clinicaltrials.gov)
P1/2, N=280, Recruiting, DualityBio Inc. | Not yet recruiting --> Recruiting
Enrollment open • Metastases
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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)
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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 • NTRK3 mutation
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BNT324
9ms
Unraveling the Mystery: Next Generation Sequencing Sheds Light on Neuroblastoma Pathogenesis and Targeted Therapies. (PubMed, Front Biosci (Landmark Ed))
This study presents valuable mutation data for relapsed and refractory NB patients. The high frequency of the ERBB2 I655V mutation may allow further exploration of this mutation as a potential therapeutic target. Rare BRAF mutations may also provide opportunities for targeted therapy. The role of ABL1 mutations in NB should also be explored further.
Journal • Next-generation sequencing
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HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ABL1 (ABL proto-oncogene 1) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR3 (Fibroblast growth factor receptor 3)
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BRAF mutation • NTRK1 fusion • HER-2 mutation • ALK fusion • ALK mutation • RET mutation • FGFR3 fusion • ALK R1275Q • HER-2 I655V • NTRK1 mutation
10ms
Overcoming MET-mediated resistance in oncogene-driven NSCLC. (PubMed, iScience)
The combination of targeted therapy with MET or SHP2 inhibitors was found to overcome MET-mediated resistance in both in vitro and in vivo assays. This study highlights the importance of considering MET overexpression as a resistance driver to NSCLC targeted therapies to better identify patients who could potentially benefit from combination approaches with MET or SHP2 inhibitors.
Journal
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • 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) • TPM3 (Tropomyosin 3)
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EGFR mutation • HER-2 overexpression • MET amplification • MET overexpression • NTRK1 mutation • MET amplification + MET overexpression
11ms
A Study of DB-1311 in Advanced/Metastatic Solid Tumors (clinicaltrials.gov)
P1/2, N=280, Not yet recruiting, DualityBio Inc.
New P1/2 trial • Metastases
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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)
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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 • NTRK3 mutation
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BNT324
1year
Selective TrkA Inhibitor VMD-928 to Treat TrkA Overexpression Driven Solid Tumors or Lymphoma (clinicaltrials.gov)
P1, N=74, Recruiting, VM Oncology, LLC | Trial completion date: Jun 2024 --> Jun 2025 | Trial primary completion date: Dec 2023 --> Dec 2024
Trial completion date • Trial primary completion date
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1)
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NTRK1 fusion • NTRK1 mutation • NTRK expression
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VMD-928
1year
Comprehensive survey of AACR GENIE cBioPortal database of receptor tyrosine kinase fusion in colorectal carcinoma identified high co-occurring genomic alterations in NTRK1 & RET fusion-positive CRC (ESMO-GI 2023)
However, ORR was the lowest among entrectinib-treated NTRK+ CRC (20%, 2/10) and selpercatinib treated RET+ CRC (20%, 2/10)...Thus, NTRK+ and RET+ CRC patients may benefit more from FDA approved immunotherapy (single agent pembrolizumab or dostarlimab) than TKIs in NTRK+ and RET+ CRC. We surveyed all 58 human RTKs to identify RTK fusions in CRC using AACR GENIE cBioPortal public version 13.0... In this comprehensive survey of human RTK fusions in CRC, NRTK1+ and RET+ CRC harbor significantly higher mean co-occurring genomic alterations compared to other RTK+ CRC consistent with previous reports. Hypothesis-generating randomized trials comparing pembrolizumab versus target-specific TKIs should be performed to address optimal treatment of NTRK1/3/RET+ CRC.
Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • FLT3 (Fms-related tyrosine kinase 3) • RET (Ret Proto-Oncogene) • FGFR2 (Fibroblast growth factor receptor 2) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR1 (Fibroblast growth factor receptor 1) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • FLT1 (Fms-related tyrosine kinase 1) • FLT4 (Fms-related tyrosine kinase 4) • NTRK (Neurotrophic receptor tyrosine kinase)
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EGFR mutation • TMB-H • MSI-H/dMMR • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • RET fusion • FGFR2 fusion • RET mutation • ROS1 fusion • FGFR1 fusion • NTRK1 mutation • NTRK1 positive • RET positive
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Keytruda (pembrolizumab) • Rozlytrek (entrectinib) • Retevmo (selpercatinib) • Jemperli (dostarlimab-gxly)
1year
The Driverless Triple-Wild-Type (BRAF, RAS, KIT) Cutaneous Melanoma: Whole Genome Sequencing Discoveries. (PubMed, Cancers (Basel))
The two regressed melanomas of this cohort shared a 17-gene mutation signature, containing genes involved in antitumor immunity and several cell surface receptors. Even with this comprehensive genomic approach, a few cases remained driverless, suggesting that unrecognized drivers are hiding among passenger mutations.
Journal • Tumor mutational burden • IO biomarker
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BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NF1 (Neurofibromin 1) • RAS (Rat Sarcoma Virus) • FLT1 (Fms-related tyrosine kinase 1)
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EGFR mutation • BRAF wild-type • NF1 mutation • RET mutation • NRAS wild-type • KIT wild-type • NTRK1 mutation • FLT1 mutation
1year
Molecular determinants of KRAS p.G12C inhibitor efficacy in advanced NSCLC (AACR 2023)
Background: Irreversible allosteric KRAS p.G12C inhibitors (KG12Ci) such as sotorasib and adagrasib have revolutionized the therapeutic landscape of advanced KG12C-mutant NSCLC, however individual responses are heterogeneous and curtailed by innate and adaptive/acquired resistance. Co-mutations in KEAP1, SMARCA4 and CDKN2A/2B define subgroups of KG12C NSCLC pts with markedly distinct outcomes with KG12Ci monotherapy. Tailoring of KG12C inhibitor-anchored therapeutic strategies and patient stratification should take into account the co-mutation status of individual tumors.
Clinical • Metastases
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • 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) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • KEAP1 (Kelch Like ECH Associated Protein 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • ATRX (ATRX Chromatin Remodeler) • DAXX (Death-domain associated protein) • PI3K (Phosphoinositide 3-kinases)
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KRAS G12C • BRAF mutation • PTEN mutation • STK11 mutation • ALK mutation • KEAP1 mutation • CDKN2A mutation • KRAS G12 • SMARCA4 mutation • NTRK1 mutation • NTRK3 mutation
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Lumakras (sotorasib) • Krazati (adagrasib)
1year
Different treatment response in several head and neck squamous cell carcinoma (HNSCC) cell lines reflecting underlying genomic and molecular signatures (AACR 2023)
PI3K/mTOR dual inhibition, PI3Kalpha inhibitor, AKT inhibitor, FGFR inhibitor, ALK/IGF1R inhibitor, CDK4/6 inhibitor, BCl2 inhibitor, WEE1 inhibitor, ATR inhibitor, DNA-PK inhibitor, AT2AR inhibitor, Mcl-1 inhibitor, MEK1/2 inhibitor, EZH2 inhibitor, HDAC inhibitor, CDK9 inhibitor, DNMT3 inhibitor, BRD4/BET inhibitor, JAK2 inhibitor, CXCR4 inhibitor, FAK inhibitor, BTK inhibitor, eribulin, & VEGFR2/ PDGFR/FGFR or VEGFR2/c-MET/Axl triple blockage might be effective on TW2.6 and reverse treatment refractoriness, maybe through the inhibition of mesenchymal transformation, pRB, & PI3K/AKT /mTOR signaling and the modulation of stemness & PD1/PDL1 pathway...All cell lines will be tried to be categorized as TCGA subtypes for the reference of future drug combinations.Cell linesSCC25KBSASCAL27FaDuSCC15SCC9SCC4TW2.6Differ- entiationWellPoorPoorPoorPoorWellWellWellWell, but rapidly replicated, with high hyper-diploidy & complex rearrangementsHPV statusHPV 16/18HPV18--HPV 16/18--HPV 6/11-EGFR statusMediumLowHighHighMediumHighLowMedium to highUnknownDocetaxel sensitivity+++++++++++++ to +++++-+Cisplatin sensitivity+++++++++++++- to +-- to +5-FU sensitivity+++++++++++-+ to ++-- to +Afatinib sensitivity+++- to +-+++++ to +++++++++-Polo-like kinase Inhibitor sensitivity+++++++++++++ to +++- to +-- to +VEGFR2 Inhibitor sensitivity----+++++--++PI3K/ mTOR inhibitorAll cell lines sensitiveCDK4/6 Inhibitor response+++- to ++++++ to +++++++++++++ to +++Western blotsWeak p-AKT & VEGF-A, mild PDL1 and BMI-1, Gli-1(+)Weak p-AKT, mild PDL1 and strong VEGF-A & BMI-1, p16(+)Moderate p-AKT & BMI-1, high PDL1, mild VEGF-AHigh p-AKT & VEGF-A, mild PDL1 & BMI-1High VEGF-A, moderate p-AKT & PDL1, weak BMI-1, Gli-1(+)Weak p-AKT & VEGF-A, mild PDL1 & BMI-1Weak p-AKT, VEGF-A, & BMI-1, moderate PDL1Moderate p-AKT & VEGF-A, strong BMI-1, mild PDL1, Gli-1(+)High p-AKT, PDL1, & VEGF-A and moderate BMI-1NGSCCND1 gain, CDKN2A deletion, FRG1 mutation, HGF mutation, p53 mutation, ATR mutation, SMO mutation, RUNX1T1 mutationSTK11 mutation, PDGFRA mutation, IGF1 mutation, BCOR mutation, EGFR mutation, NOTCH1 mutation, MET mutation, IKZF1 mutation, NFKB1 mutation, DPYD mutation, FGFR4 mutation, BRCA1 mutation, MSH2 mutation, DNMT3A mutationKRAS mutation, MDM2 mutation, TMB-H, AXIN1 loss, RAD51D mutation, NOTCH1/2 mutation, ERBB4 mutation, PALB2 mutation, p53 mutation, POLE mutation, CASP8 mutation, BRCA2 mutation, RNF43 mutation, LRP1B mutation, MET mutationCDKN2A deletion, EGFR amplification, SMAD4 mutation, TMB-H, LRP1B mutation, APC mutation, CASP8 mutation, CREBBP mutation, PIK3CG mutation, NRAS mutation, ABL1 mutation, FGF23 mutation, HGF mutation, ATRX mutation, p53 mutation, ERBB2 mutation, ROS1 mutation, EP300 mutation, NRAS mutation, CDKN1A mutation, KDM6A mutation, FLT4 mutationCCND1 gain, CDKN2A deletion, FLCN mutation, TMB-H, LRP1B mutation, SMAD4 loss, SF3B1 mutation, FAT1 mutation, VHL mutation, NOTCH3 mutation, EPHA5 mutation, p53 mutation, ERCC2 mutationCCND1 gain, EGFR amplification, SMO mutation, ATR mutation, FAT1 loss, NTRK1 mutation, KMT2D mutation, p53 mutation, NOTCH3 mutationCDKN2A deletion, AXIN2 amplification, SMAD3 loss, HRAS mutation, ATR mutation, NF1 mutation. IGF1R mutation, FLCN mutation, KEAP1 mutation, ASXL1 mutation, PMS2 mutationCCND1 gain, NF1 loss, LRP1B mutation, NSD1 mutation, KMT2D mutation, p53 mutation, EPHA2 mutationFAT1 loss, CCND3/FGF10 amplification, PIK3CA H1047R mutation, STK11 mutation, RICTOR/FLCN amplification, VEGF-A amplification , TSC2 mutation, EPHB1 mutation, MAP2K4 mutation, KDM5A mutation, PDGFRB mutation, SETD2 mutation, RPTOR mutation, APC mutation, DDR2 mutation, ATM mutation, MDM2 mutation, p53 mutation, CDK12 mutation, HRAS mutation, MYC mutation, CDK8 mutation, ARID1B lossOutcomesBest; like TCGA CL (HPV+) subtypeLike TCGA basal subtype, but responded to particular treatments eachBasalBasalLike TCGA mesen-chymal subtype (HPV+)Like TCGA CL(HPV-) subtype, different characters between these 3 cell linesCL(HPV-) subtypeCL(HPV-) subtypeWorse; like TCGA EMT subtype (HPV-)Potential treatmentsAll sensitive maybe; Hedgehog inhibitor , HGF/c-MET inhibitor, and I/O could be tried(1) Taxane, cisplatin, PLKi (2) mTORi (3) IGF1Ri, METi, PDGFRi, FGFRi (4) Epigenetics (5) I/O(1) Taxane, cisplatin, 5-FU, PLKi (2) CDK4/6i (3) I/O (4) DDRi (5) KRASi, METi, HERi (6) p53 reactivator and MDM2/Mcl-1 inhibitor(1) Taxane, cisplatin, 5-FU, PLKi (2) CDK4/6i (3) Mild EGFRi response (4) I/O (5) NRASi, FGFRi, HGF/c-METi/ROS1i/HERi (6) p53 reactivator/DDRi/Epigenetics(1) Cisplatin, 5-FU (2) EGFRi and VEGFR2i (3) Weak to PLKi & CDK4/6i (4) I/O (5) mTORi (6) Ephi (7) DDR/Epigenetics (8) p53 reactivator (9) HIFi(1) Taxane and PLKi (2) EGFRi, VEGFR2i, CDK4/6i (3) NTRKi (4) Hedgehog inhibitor (5) DDRi, epigenetics,& p53 reactivator(1) Taxane &5-FU (2) EGFRi (3) HRASi (4) DDRi/Epigenetics (5) I/O (6) IGF1Ri (7) mTORi(1) EGFRi (2) CDK4/6i (3) I/O (4) Epigenetics (5) Ephi (6) p53 reactivator(1) CDK4/6 inhibitor (2) Multi-targeted VEGFR TKI (3) PI3K/AKT/mTOR inhibitor (4) ICIs combination (5) p53 reactivator/ DDR interventions/Epigenetics (6) Dasatinib, HRASi, EphB1/B4 interventions Further NGS analysis may translate these HNSCC cell lines to represent TCGA subtypes for the reference of future drug combinations, esp... Further NGS analysis may translate these HNSCC cell lines to represent TCGA subtypes for the reference of future drug combinations, esp. immunotherapy, basic/translational research, and animal models. LRP1B will be a potential ICIs efficacy biomarker in HNSCC.
Preclinical • Tumor mutational burden • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • ATM (ATM serine/threonine kinase) • STK11 (Serine/threonine kinase 11) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • DNMT3A (DNA methyltransferase 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NOTCH1 (Notch 1) • NF1 (Neurofibromin 1) • KEAP1 (Kelch Like ECH Associated Protein 1) • POLE (DNA Polymerase Epsilon) • AXL (AXL Receptor Tyrosine Kinase) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • CCND1 (Cyclin D1) • MDM2 (E3 ubiquitin protein ligase) • PALB2 (Partner and localizer of BRCA2) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • KMT2D (Lysine Methyltransferase 2D) • LRP1B (LDL Receptor Related Protein 1B) • FGFR4 (Fibroblast growth factor receptor 4) • MSH2 (MutS Homolog 2) • RNF43 (Ring Finger Protein 43) • CDK12 (Cyclin dependent kinase 12) • SMAD4 (SMAD family member 4) • IKZF1 (IKAROS Family Zinc Finger 1) • ERCC2 (Excision repair cross-complementation group 2) • PMS2 (PMS1 protein homolog 2) • VHL (von Hippel-Lindau tumor suppressor) • APC (APC Regulator Of WNT Signaling Pathway) • ATRX (ATRX Chromatin Remodeler) • TSC2 (TSC complex subunit 2) • IGF1R (Insulin-like growth factor 1 receptor) • NOTCH2 (Notch 2) • CREBBP (CREB binding protein) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • SMO (Smoothened Frizzled Class Receptor) • BCOR (BCL6 Corepressor) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • FAT1 (FAT atypical cadherin 1) • KDM6A (Lysine Demethylase 6A) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • PIK3CG (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Gamma) • NOTCH3 (Notch Receptor 3) • ARID1B (AT-Rich Interaction Domain 1B) • EP300 (E1A binding protein p300) • FLT4 (Fms-related tyrosine kinase 4) • IGF1 (Insulin-like growth factor 1) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1) • RAD51D (RAD51 paralog D) • RICTOR (RPTOR Independent Companion Of MTOR Complex 2) • EPHA2 (EPH receptor A2) • BMI1 (BMI1 proto-oncogene, polycomb ring finger) • CASP8 (Caspase 8) • CCND3 (Cyclin D3) • BRD4 (Bromodomain Containing 4) • DDR2 (Discoidin domain receptor 2) • FLCN (Folliculin) • KDM5A (Lysine Demethylase 5A) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • DPYD (Dihydropyrimidine Dehydrogenase) • EPHA5 (EPH Receptor A5) • EPHB1 (EPH Receptor B1) • FGF10 (Fibroblast Growth Factor 10) • FGF23 (Fibroblast Growth Factor 23) • MAP2K4 (Mitogen-Activated Protein Kinase Kinase 4) • SMAD3 (SMAD Family Member 3)
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TP53 mutation • KRAS mutation • BRCA2 mutation • BRCA1 mutation • EGFR mutation • TMB-H • NRAS mutation • PIK3CA mutation • EGFR amplification • ATM mutation • PIK3CA H1047R • STK11 mutation • DNMT3A mutation • PALB2 mutation • POLE mutation • NF1 mutation • NOTCH1 mutation • ASXL1 mutation • CDKN2A deletion • BCL2 overexpression • KEAP1 mutation • SF3B1 mutation • CDKN2A mutation • KMT2D mutation • CDK12 mutation • LRP1B mutation • VHL mutation • PIK3CA amplification • HRAS mutation • APC mutation • ATR mutation • ATRX mutation • CCND1 amplification • PDGFRA mutation • CREBBP mutation • MSH2 mutation • RNF43 mutation • ROS1 mutation • SMAD4 mutation • BCOR mutation • FGFR4 mutation • KDM6A mutation • RAD51D mutation • TSC2 mutation • FAT1 mutation • MYC mutation • ARID1B mutation • NOTCH3 mutation • PMS2 mutation • SMO mutation • IKZF1 mutation • MDM2 mutation • NTRK1 mutation • EP300 mutation • ERBB4 mutation • NSD1 mutation • PIK3CA H1047R + PIK3C2B amplification • PIK3CG mutation • SETD2 mutation • EPHA5 mutation • EPHB1 mutation • ERCC2 mutation • FGF10 amplification • FGF23 mutation • FLCN mutation • HGF mutation • PDGFRB mutation • RAD51 mutation
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cisplatin • Gilotrif (afatinib) • dasatinib • 5-fluorouracil • Halaven (eribulin mesylate)
1year
Treatment prognostic signature of patients with non-small cell lung cancer: a retrospective single-institutional study (AACR 2023)
NSCLC patients’ responses to specific treatments are diverse because of tumor heterogeneity. Our work demonstrates how analyzing patients’ sequencing data facilitates the clinical selection of optimized treatment strategies.
Retrospective data • IO biomarker
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • NOTCH1 (Notch 1) • CDK4 (Cyclin-dependent kinase 4) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • GATA3 (GATA binding protein 3)
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KRAS mutation • BRAF mutation • NTRK1 mutation
over1year
Genetic testing and prognosis of sarcomatoid hepatocellular carcinoma patients. (PubMed, Front Oncol)
The potentially actionable mutations of driver genes may provide more therapeutic options for SHC. Survival analysis found that age, smoking, drinking, and tumor diameter may be independent prognostic predictors of SHC.
Journal • Tumor mutational burden • BRCA Biomarker
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KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1)
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TP53 mutation • BRCA2 mutation • BRCA1 mutation • NTRK1 fusion • NTRK1 mutation
over1year
Genomic and transcriptomic analysis of MSI-H colorectal cancer patients with targetable alterations identifies clinical implications for immunotherapy. (PubMed, Front Immunol)
Our study preliminary revealed MSI-H altered as a novel subtype of MSI-H CRC patients with unique molecular signatures and immune-active tumor microenvironment. Given the accessibility of immune checkpoint inhibitors (ICIs) treatment, our results might provide clinical evidence for immunotherapy in MSI-H CRC patients with targetable alterations.
Journal • Tumor mutational burden • MSi-H Biomarker • IO biomarker
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TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • IFNG (Interferon, gamma) • TGFB1 (Transforming Growth Factor Beta 1) • NTRK (Neurotrophic receptor tyrosine kinase)
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BRAF V600E • MSI-H/dMMR • BRAF V600 • FGFR2 mutation • NTRK1 mutation • NTRK fusion
over1year
Characterization of Molecular Divers in 554 Consecutive Papillary Thyroid Carcinomas in a Post-2017 WHO Classification Cohort (USCAP 2023)
In this post-2017 WHO classification cohort of 554 consecutive PTCs, BRAF V600E mutation is highly prevalent in 87% of the cases. RAS mutations account for only 1.1% of the cases and half of them are classified as encapsulated follicular variant of PTC. Kinase gene fusions are identified in 8.5% of the cases and are clinically relevant given the emerging targeted kinase inhibitor therapy.
KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RET (Ret Proto-Oncogene) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR1 (Fibroblast growth factor receptor 1) • HRAS (Harvey rat sarcoma viral oncogene homolog)
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BRAF V600E • KRAS mutation • NRAS mutation • BRAF V600 • NTRK1 fusion • NTRK3 fusion • RET fusion • ALK fusion • RAS mutation • NRAS Q61K • HRAS mutation • NRAS Q61 • BRAF fusion • NRAS Q61R • FGFR1 fusion • NTRK1 mutation • HRAS Q61R • KRAS Q61K
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FusionPlex® Pan Solid Tumor v2 panel • VENTANA anti-BRAF V600E (VE1) Mouse Monoclonal Primary Antibody
over1year
Distinct gene mutation profiles among multiple and single primary lung adenocarcinoma. (PubMed, Front Oncol)
We compared the mutation landscape of MP-LUAD and SP-LUAD and identified six differentially mutated genes (RBM10, CDK4, ATRX, NTRK1, PREX2, SS18), and certain SNV loci in TP53 and EGFR which might play key roles in lineage decomposition in multifocal samples. These findings may provide insight into personalized prognosis prediction and new therapies for MP-LUAD patients.
Journal
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EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • CDK4 (Cyclin-dependent kinase 4) • ATRX (ATRX Chromatin Remodeler) • RBM10 (RNA Binding Motif Protein 10) • PREX2 (Phosphatidylinositol-3,4,5-Trisphosphate Dependent Rac Exchange Factor 2) • SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex)
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TP53 mutation • NTRK1 mutation • RBM10 mutation • CDK4 mutation
almost2years
New P1/2 trial
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BRAF (B-raf proto-oncogene) • MET (MET proto-oncogene, receptor tyrosine kinase) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)
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PD-L1 expression • BRAF V600E • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • MET mutation • RET rearrangement • NTRK1 mutation • NTRK3 mutation
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AP203
almost2years
Integrative Genomic and Transcriptomic Analysis of Primary Malignant Gliomas Revealed Different Patterns Between Grades and Somatic Mutations Related to Glioblastoma Prognosis. (PubMed, Front Mol Biosci)
Taken together, our molecular data revealed that GBM patient showed distinct characteristics related to individual gene, chromosome integrity, and infiltrating immune cells compared to LGG (grade II/III) patients. We also identified few novel genes with SNV or CNV, which might be the potential markers for clinical outcome of GBM.
Journal
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • B2M (Beta-2-microglobulin) • PKD1 (Polycystin 1) • PRKD1 (Protein Kinase D1)
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NTRK1 mutation
almost2years
Patient-derived tumor organoids for personalized medicine in a patient with rare hepatocellular carcinoma with neuroendocrine differentiation: a case report. (PubMed, Commun Med (Lond))
Based on the results of the in vitro drug screening, etoposide and carboplatin are used as first line palliative combination treatment. With genomic analysis revealing a NTRK1-mutation of unknown significance (kinase domain) and tumor organoids found to be sensitive to entrectinib, a pan-TRK inhibitor, the patient was treated with entrectinib as second line therapy...The rapid establishment of patient-derived tumor organoids allows in vitro drug testing and thereby personalized treatment choices, however clinical translation remains a challenge. To the best of our knowledge, this report provides a first proof-of-principle for using organoids for personalized medicine in this rare subtype of primary liver cancer.
Journal
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • SYP (Synaptophysin)
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NTRK1 mutation
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carboplatin • Rozlytrek (entrectinib) • etoposide IV
2years
Driver coexistence characteristics of ALK-fusion in Chinese patients with lung cancer. (ASCO 2022)
In this cohort, very few of ALK fusion patients coexisted with other driver mutations. Among the co-existence samples, ALK fusion were mainly coexisting with the site mutations of EGFR and KRAS, amplifications of MET and ERBB2, fusions of ROS1 and RET. These samples maybe obtain more effective outcomes by combined or sequential therapies.
Clinical
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • 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) • EML4 (EMAP Like 4) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)
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KRAS mutation • EGFR mutation • KRAS G12C • BRAF mutation • HER-2 amplification • EGFR L858R • EGFR exon 19 deletion • MET amplification • RET fusion • MET exon 14 mutation • ALK fusion • ALK mutation • RET mutation • ROS1 fusion • MET mutation • KRAS G12 • EGFR G719S • KRAS amplification • NTRK1 mutation • KRAS exon 4 mutation
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Onco PanScan™
2years
Characterization of NTRK alterations in metastatic colorectal cancer. (ASCO 2022)
NTRK gene fusion is a relatively rare event ( 10). Hypermutator tumors cause frequent VUS alterations in the NTRK gene with unknown clinical relevance.
Tumor Mutational Burden • MSi-H Biomarker
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TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • POLE (DNA Polymerase Epsilon) • POLD1 (DNA Polymerase Delta 1) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
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TMB-H • MSI-H/dMMR • NTRK1 fusion • TMB-L • NTRK1 mutation • NTRK fusion
2years
Selective TrkA Inhibitor VMD-928 to Treat TrkA Overexpression Driven Solid Tumors or Lymphoma (clinicaltrials.gov)
P1, N=74, Recruiting, VM Oncology, LLC | N=54 --> 74 | Trial completion date: Dec 2022 --> Jun 2024 | Trial primary completion date: Jun 2022 --> Dec 2023
Enrollment change • Trial completion date • Trial primary completion date
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1)
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NTRK1 fusion • NTRK1 mutation • NTRK expression
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VMD-928
2years
Stress, Thyroid Dysregulation and Thyroid Cancer in Children and Adolescents. Proposed Impending Mechanisms. (PubMed, Horm Res Paediatr)
Aberrant methylation of tumour suppressor genes such as P16INK4A, RASSF, PTEN is associated with PTC; histone H3 acetylation is shown to be higher in TC, and thyroid specific non-coding-RNAs are downregulated in PTC. This review focuses on the above proposed mechanisms that potentially lead to thyroid tumorigenesis with the aim to help in the development of novel prognostic and therapeutic strategies for TC.
Review • Journal
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BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)
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BRAF mutation • PIK3CA mutation • PTEN mutation • RET mutation • NTRK1 mutation
2years
Inhibition of EGFR and MEK surmounts entrectinib resistance in a brain metastasis model of NTRK1-rearranged tumor cells. (PubMed, Cancer Sci)
These results indicate that resistant mutations, such as NTRK1-G595R, and alternative pathway activation, such as ERK activation, could simultaneously occur in entrectinib-resistant tumors, thereby causing resistance to second-generation inhibitor repotrectinib. These findings highlight the importance of intensive examinations to identify resistance mechanisms and application of the appropriate combination treatment to circumvent the resistance.
Journal
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EGFR (Epidermal growth factor receptor) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK1 mutation • NTRK1 G595R
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Rozlytrek (entrectinib) • Augtyro (repotrectinib)
over2years
Entrectinib Induces Apoptosis and Inhibits the Epithelial-Mesenchymal Transition in Gastric Cancer with NTRK Overexpression. (PubMed, Int J Mol Sci)
Entrectinib treatment significantly reduced expression levels of phosphorylated NFκB, AKT, ERK, and β-catenin in NCI-N87 and AGS cells, whereas it upregulated the expression levels of ECAD in NCI-N87 cells. Together, these results suggest that entrectinib has anti-cancer activity not only in GC cells overexpressing pan NTRK but also in VEGFR2 GC cells via the inhibition of the pan NTRK and VEGFR signaling pathways.
Journal
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PD-L1 (Programmed death ligand 1) • 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) • TGFBR1 (Transforming Growth Factor Beta Receptor 1)
|
PD-L1 expression • KDR expression • NTRK1 mutation • NTRK3 mutation • NTRK expression
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Rozlytrek (entrectinib)
over2years
Unique genomic alterations of cerebrospinal fluid cell-free DNA are critical for targeted therapy of non-small cell lung cancer with leptomeningeal metastasis. (PubMed, Genomics)
Others such as ROS1 rearrangement, RET fusion, HER2 mutation, NTRK1 fusion, and BRAF V600E mutation were detected in 7.9% of CSF and 11.1% of tumor tissues, but only 4% in plasma. Our study has shed light on the unique genomic variations of CSF and demonstrated that CSF may represent better liquid biopsy for NSCLC patients with LM.
Journal
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • 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)
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BRAF V600E • EGFR mutation • BRAF V600 • NTRK1 fusion • HER-2 mutation • RET fusion • ROS1 fusion • ROS1 rearrangement • RET rearrangement • ALK translocation • NTRK1 mutation
over2years
Unique Genomic Alterations of Cerebrospinal Fluid Cell-Free DNA Are Critical for Targeted Therapy of Non-Small Cell Lung Cancer With Leptomeningeal Metastasis. (PubMed, Front Oncol)
Others such as ROS1 rearrangement, RET fusion, HER2 mutation, NTRK1 fusion, and BRAF V600E mutation were detected in 7.9% of CSF and 11.1% of tumor tissues but only 4% in plasma. Our study has shed light on the unique genomic variations of CSF and demonstrated that CSF might represent better liquid biopsy for NSCLC patients with LM.
Journal
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • 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)
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BRAF V600E • EGFR mutation • BRAF V600 • NTRK1 fusion • HER-2 mutation • RET fusion • ROS1 fusion • ROS1 rearrangement • RET rearrangement • ALK translocation • NTRK1 mutation
almost3years
Clinical • New P1/2 trial • Combination therapy
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ALK (Anaplastic lymphoma 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) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK1 fusion • NTRK3 fusion • ROS1 fusion • ALK amplification • NTRK1 mutation
|
temozolomide • irinotecan • Augtyro (repotrectinib)
almost3years
The genomic characteristics of different progression patterns in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors. (PubMed, Ann Transl Med)
Mutations in RAD54L (P=0.018) and MYC (P=0.04) were more common in FP patients; HPD patients showed more frequent RAD54L mutations (P<0.001). We demonstrated different genomic characteristics across different progression patterns following ICI treatment, which might assist clinicians in the prediction of a patient's response, identifying candidates for more effective ICI therapy.
Clinical • Journal • Checkpoint inhibition • Tumor Mutational Burden • IO biomarker
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • CDKN1B (Cyclin dependent kinase inhibitor 1B)
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KRAS mutation • EGFR mutation • HER-2 amplification • HER-2 mutation • MET amplification • RET fusion • EGFR amplification • ALK fusion • ALK mutation • MET mutation • ATRX mutation • ALK amplification • NTRK1 mutation • RAD54L mutation
3years
[VIRTUAL] NTRK genomic alterations in Latin-American cancer patients. (ASCO 2021)
"NTRK alterations are rare events in Latin-American cancer patients . In 3 series including 1,795 patients, 31 somatic variants were detected . No NTRK fusions or CNVs were identified ."
Clinical
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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 • NTRK1 mutation • NTRK fusion
|
Oncomine Focus Assay
3years
A novel NCOR2-NTRK1 fusion detected in a patient of lung adenocarcinoma and response to larotrectinib: a case report. (PubMed, BMC Pulm Med)
Altogether, this report provided a new driver of lung adenocarcinoma expanded the mutational spectrum of NTRK1 fusion variants and suggested using larotrectinib as the targeted therapy is more effective than anti-PD-1 inhibitor in lung adenocarcinoma harboring with NTRK fusion, positive PD-L1 expression, and high TMB simultaneously.
Clinical • Journal • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NCOR2 (Nuclear Receptor Corepressor 2) • NTRK (Neurotrophic receptor tyrosine kinase)
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PD-L1 expression • TMB-H • PD-L1 overexpression • NTRK1 fusion • NTRK1 mutation • NTRK fusion
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Vitrakvi (larotrectinib) • AiRuiKa (camrelizumab)
3years
Identification of NTRK gene fusions in lung adenocarcinomas in the Chinese population. (PubMed, J Pathol Clin Res)
According to this study's results, they are independent oncogenic drivers, mutually exclusive with other driver mutations. We demonstrated that NTRK rearrangement analysis using a DNA-based approach should be verified with an RNA-based assay.
Clinical • Journal
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • KIF5B (Kinesin Family Member 5B) • TPM3 (Tropomyosin 3) • SQSTM1 (Sequestosome 1) • NTRK (Neurotrophic receptor tyrosine kinase)
|
NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • TPM3-NTRK1 fusion • NTRK1 mutation • NTRK fusion
3years
[VIRTUAL] More somatic mutations can be detected in cerebrospinal fluid ctDNA of NSCLC patients with brain metastases (AACR 2021)
Compared with plasma ctDNA, cerebrospinal fluid ctDNA can detect more somatic mutations in NSCLC patients with brain metastases, which can provide more comprehensive guidance for targeted therapy of brain metastases.
Clinical • Circulating tumor DNA
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • LRP1B (LDL Receptor Related Protein 1B) • CDK4 (Cyclin-dependent kinase 4) • RICTOR (RPTOR Independent Companion Of MTOR Complex 2)
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TP53 mutation • EGFR mutation • BRAF mutation • HER-2 amplification • NTRK1 fusion • EGFR L858R • EGFR T790M • EGFR amplification • PIK3CA amplification • NTRK1 mutation