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BIOMARKER:

NRG1 fusion

i
Other names: NRG1, GGF, HGL, HRG, NDF, NRG1-IT2, Neuregulin 1, Heregulin
Entrez ID:
14d
Zenocutuzumab: First Approval. (PubMed, Drugs)
On 4 December 2024, zenocutuzumab received its first approval in the USA for the treatment of adults with advanced, unresectable or metastatic pancreatic adenocarcinoma or non-small cell lung cancer (NSCLC) harbouring an NRG1 gene fusion with disease progression on or after prior systemic therapy. This article summarizes the milestones in the development of zenocutuzumab leading to this first approval for the second-line treatment of NRG1+ pancreatic adenocarcinoma or NSCLC.
Review • Journal
|
HER-2 (Human epidermal growth factor receptor 2) • NRG1 (Neuregulin 1)
|
NRG1 fusion
|
Bizengri (zenocutuzumab-zbco)
18d
Journal
|
NRG1 (Neuregulin 1)
|
NRG1 fusion
|
Bizengri (zenocutuzumab-zbco)
29d
Molecular tissue profiling in a clinically selected pancreatic cancer cohort. (PubMed, Oncol Res Treat)
The high frequency of targetable alterations in our cohort underscores upfront NGS testing in PDAC. Younger patients, those with a positive FH and KRAS WT patients should be of particular interest.
Journal • BRCA Biomarker • PARP Biomarker
|
KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • NRG1 (Neuregulin 1) • ATP1B1 (ATPase Na+/K+ transporting subunit beta 1)
|
TP53 mutation • KRAS mutation • MSI-H/dMMR • KRAS wild-type • RAS wild-type • NRG1 fusion
|
Lynparza (olaparib) • 5-fluorouracil • irinotecan • leucovorin calcium
1m
Efficacy of Zenocutuzumab in NRG1 Fusion-Positive Cancer. (PubMed, N Engl J Med)
Zenocutuzumab showed efficacy in patients with advanced NRG1 fusion-positive cancer, notably NSCLC and pancreatic cancer, with mainly low-grade adverse events. (Funded by Merus; eNRGy ClinicalTrials.gov number, NCT02912949.).
Journal
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HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1)
|
NRG1 fusion
|
Bizengri (zenocutuzumab-zbco)
1m
A Study of Zenocutuzumab (MCLA-128) in Patients With Solid Tumors Harboring an NRG1 Fusion (eNRGy) (clinicaltrials.gov)
P2, N=250, Active, not recruiting, Merus N.V. | Recruiting --> Active, not recruiting
Enrollment closed
|
NRG1 (Neuregulin 1)
|
NRG1 fusion
|
Bizengri (zenocutuzumab-zbco)
1m
NRG1 Fusions: The New Kid on the Block. (PubMed, Curr Oncol Rep)
Zenocutuzumab, a bispecific antibody targeting HER2 and HER3, is the first FDA approved treatment for previously treated NRG1 fusion-positive NSCLC and pancreatic cancer...NRG1 fusions are rare molecular drivers of NSCLC that can be effectively treated with targeted therapies. Here, we summarize the biology and detection of NRG1 fusions, the currently approved bispecific antibody used to treat NRG1 fusion-positive NSCLC, and new agents under investigation.
Review • Journal
|
HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1)
|
NRG1 fusion
|
Bizengri (zenocutuzumab-zbco)
2ms
Enhanced detection of actionable mutations in NSCLC through pleural effusion cell-free DNA sequencing: A prospective study. (PubMed, Eur J Cancer)
PE cfDNA genotyping has clinical applicability for NSCLC patients and can serve as an additional source for molecular testing. Incorporating PE NGS cfDNA analysis into genetic testing enhances diagnostic yield and aids in identifying actionable mutations in clinical practice.
Journal • Pleural effusion
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NRG1 (Neuregulin 1) • CD74 (CD74 Molecule)
|
KRAS mutation • EGFR mutation • KRAS G12C • EGFR L858R • HER-2 mutation • EGFR exon 19 deletion • EGFR exon 20 insertion • ALK rearrangement • HER-2 exon 20 insertion • ROS1 rearrangement • NRG1 fusion • RET rearrangement • KRAS G12 • CD74-NRG1 fusion • EGFR rearrangement • NRG1 fusion
3ms
Emerging molecular phenotypes and potential therapeutic targets in esophageal and gastric adenocarcinoma unearthed by whole genome and transcriptome analyses. (PubMed, Pathol Res Pract)
Our findings support the potential of whole genome and transcriptome sequencing analyses as a comprehensive approach to identify treatment targets in adenocarcinoma of the stomach and the esophagus, and their application in precision oncology.
Journal
|
ALK (Anaplastic lymphoma kinase) • HRD (Homologous Recombination Deficiency) • NRG1 (Neuregulin 1) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • NTRK (Neurotrophic receptor tyrosine kinase)
|
HRD • NRG1 fusion • RAD51B mutation • MET fusion
4ms
Advances in the Treatment of Rare Mutations in Non-Small Cell Lung Cancer. (PubMed, Onco Targets Ther)
Some of these targeted therapies have already been approved by the Food and Drug Administration (FDA), and many others are currently undergoing clinical trials. This review summarizes recent advances in NSCLC treatment with molecular targets, highlighting progress, challenges, and their impact on patient prognosis.
Review • Journal
|
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) • NRG1 (Neuregulin 1) • NTRK (Neurotrophic receptor tyrosine kinase)
|
KRAS mutation • EGFR mutation • KRAS G12C • BRAF mutation • HER-2 mutation • RET fusion • ALK rearrangement • RET mutation • ROS1 fusion • ROS1 rearrangement • MET mutation • NRG1 fusion • KRAS G12 • NRG1 fusion • NTRK fusion
4ms
Case report: High grade serous fallopian tube carcinoma with rare NRG1 gene fusion presenting as widespread peritoneal carcinomatosis. (PubMed, Front Oncol)
Twenty-five additional tumors were found to demonstrate NRG1 fusions, including 20 new genes partners that had not been previously identified in gynecologic carcinomas. Overall, NRG1 fusion events are rare in ovarian, fallopian tube, and primary peritoneal carcinomas, but they may carry diagnostic significance in the context of borderline/low grade serous tumors, which demonstrated exclusively CLU::NRG1 fusions, and could have important predictive implications for response to ERBB/ERBB2/ERBB3-directed therapies.
Journal
|
HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1)
|
NRG1 fusion • NRG1 fusion
4ms
Redefining pancreatic cancer management with tumor-agnostic precision medicine. (PubMed, Carcinogenesis)
Despite the rarity of NTRK fusions in pancreatic cancer, larotrectinib and entrectinib have exhibited effectiveness in NTRK fusion-positive pancreatic cancers. Additionally, repotrectinib, a next-generation NTRK inhibitor, has shown promising activity in NTRK positive pancreatic cancer patients who have developed acquired resistance to previous NTRK inhibitors. Immune checkpoint inhibitors, such as pembrolizumab and dostarlimab, have proven to be effective in dMMR/MSI-H pancreatic cancers...It is crucial to continue implementing comprehensive screening strategies that encompass the ability to detect all these tumor-agnostic biomarkers. This will be essential in identifying pancreatic cancer patients who may benefit from these therapies.
Journal • BRCA Biomarker • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker • Pan tumor
|
HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • RET (Ret Proto-Oncogene) • FGFR2 (Fibroblast growth factor receptor 2) • NRG1 (Neuregulin 1) • NTRK (Neurotrophic receptor tyrosine kinase)
|
TP53 mutation • KRAS mutation • BRCA2 mutation • BRCA1 mutation • MSI-H/dMMR • KRAS G12C • HER-2 overexpression • BRAF mutation • BRAF V600 • RET fusion • FGFR2 mutation • FGFR2 fusion • ALK fusion • NRG1 fusion • KRAS G12 • NTRK positive • NTRK fusion
|
Keytruda (pembrolizumab) • Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • Jemperli (dostarlimab-gxly) • Augtyro (repotrectinib)
4ms
Prevalence, Treatment, and Outcomes of Real-World Fusion/Isoform-Positive Non-small-Cell Lung Cancer in Southern Alberta (AMP 2024)
Archer FusionPlex testing is a sensitive method of identifying recurrent and novel alterations in lung adenocarcinomas that are therapeutically actionable. Assessment of fusion/isoform-driven tumors demonstrates these alterations are acted upon. Public funding for all level 1 targeted therapies should be considered if the maximum benefit is to be derived from biomarker testing.
Real-world evidence • Clinical • Real-world
|
ALK (Anaplastic lymphoma kinase) • NRG1 (Neuregulin 1) • NKX2-1 (NK2 Homeobox 1)
|
ALK fusion • NRG1 fusion
|
FusionPlex® Dx
4ms
New P1 trial • Metastases
|
KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • PGR (Progesterone receptor) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1) • NTRK (Neurotrophic receptor tyrosine kinase)
|
KRAS mutation • EGFR mutation • KRAS G12C • BRAF mutation • HER-2 amplification • HER-2 negative • BRAF V600 • HER-2 expression • ALK positive • MET amplification • ALK fusion • ERBB3 expression • RET mutation • ROS1 fusion • MET mutation • NRG1 fusion • RET rearrangement • KRAS G12 • KRAS amplification • ER expression • PGR expression • ALK-ROS1 fusion • NRG1 fusion • NTRK fusion
5ms
Enrollment change • Metastases
|
ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1)
|
ERBB3 expression • RAS wild-type • NRG1 fusion • ERBB3 overexpression
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Xtandi (enzalutamide) • HMBD-001
5ms
NRG1 Fusions in NSCLC: Being eNRGy Conscious. (PubMed, Lung Cancer (Auckl))
Novel treatment approaches targeting the HER2/HER3 pathway are under investigation. Here, we discuss the biology and detection of NRG1 fusions in NSCLC and promising targeted treatment strategies for tumors harboring the mutation.
Review • Journal • IO biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1)
|
NRG1 fusion • NRG1 fusion
5ms
Study Evaluating Zenocutuzumab in Patients with or Without Molecularly Defined Cancers (clinicaltrials.gov)
P2, N=90, Active, not recruiting, Merus N.V. | Recruiting --> Active, not recruiting
Enrollment closed
|
NRG1 (Neuregulin 1)
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NRG1 fusion
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Gilotrif (afatinib) • Xtandi (enzalutamide) • abiraterone acetate • Bizengri (zenocutuzumab-zbco)
6ms
CRESTONE: Study of Seribantumab in Adult Patients with NRG1 Gene Fusion Positive Advanced Solid Tumors (clinicaltrials.gov)
P2, N=54, Terminated, Elevation Oncology | Trial completion date: Mar 2025 --> Feb 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Jan 2025 --> Feb 2024; Business decision
Trial completion date • Trial termination • Trial primary completion date • Metastases
|
NRG1 (Neuregulin 1)
|
NRG1 fusion
|
seribantumab (MM-121)
6ms
Emerging Tumor-Agnostic Molecular Targets. (PubMed, Mol Cancer Ther)
Emerging biomarkers with the potential for clinical actionability across tumor types include gene fusions involving NRG1, FGFR1/2/3, BRAF, and ALK, mutations in TP53 Y220C, KRAS G12C, FGFR2/3, and BRAF non-V600 (Class II). We explore the growing evidence for clinical actionability of these biomarkers in patients with advanced solid tumors.
Journal • Pan tumor
|
KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR1 (Fibroblast growth factor receptor 1) • NRG1 (Neuregulin 1)
|
TP53 mutation • KRAS mutation • KRAS G12C • BRAF mutation • FGFR2 mutation • FGFR2 fusion • ALK fusion • ALK mutation • NRG1 fusion • KRAS G12 • FGFR1 fusion • TP53 Y220C
6ms
Clinical relevance and druggability of sole reciprocal kinase fusions: A large-scale study. (PubMed, Cancer Med)
This inaugural multicenter study introduces a novel algorithm for detecting and treating sole reciprocal fusions in advanced cancers, expanding the patient population potentially amenable to KIs.
Clinical • Journal
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EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • 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) • NRG1 (Neuregulin 1) • NTRK (Neurotrophic receptor tyrosine kinase)
|
NTRK1 fusion • NTRK2 fusion • ALK fusion • ROS1 positive • NRG1 fusion
6ms
Zongertinib (BI 1810631), an irreversible HER2 TKI, spares EGFR signaling and improves therapeutic response in preclinical models and patients with HER2-driven cancers. (PubMed, Cancer Discov)
Zongertinib potently and selectively blocks HER2, while sparing EGFR, and inhibits the growth of cells dependent on HER2 oncogenic driver events, including HER2-dependent human cancer cells resistant to trastuzumab deruxtecan. Zongertinib displays potent anti-tumor activity in HER2-dependent human NSCLC xenograft models and enhances the activities of antibody-drug conjugates and KRASG12C inhibitors, without causing obvious toxicities. The preclinical efficacy of zongertinib translates in objective responses in patients with HER2-dependent tumors, including cholangiocarcinoma (SDC4-NRG1 fusion) and breast cancer (V777L HER2 mutation) thus supporting the ongoing clinical development of zongertinib.
Preclinical • Journal
|
HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • NRG1 (Neuregulin 1) • SDC4 (Syndecan 4)
|
HER-2 mutation • NRG1 fusion • HER-2 V777L • NRG1 fusion • SDC4-NRG1 fusion
|
Enhertu (fam-trastuzumab deruxtecan-nxki) • zongertinib (BI 1810631)
8ms
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.
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
8ms
RRAS and RRAS2 Mutations Are Oncogenic Drivers in Lung Cancer and are Sensitive to the Pan-RAS Inhibitor RMC-6236 (IASLC-WCLC 2024)
ERK1/2 (ulixertinib and SCH772984), MEK1/2 (binimetinib), and PI3K (pictilisib) inhibitors inhibited growth of RRAS Q87L or RRAS2 Q72L cells more potently than cells expressing wildtype proteins. Oncogenic R RAS/RRAS2 mutations were detected in LUAD at a rate similar to some other well-characterized lung cancer drivers, such as HRAS/NRAS hotspot mutations or NRG1 fusions. Our study supports the inclusion of RRAS /RRAS2 into routine molecular diagnostic protocols for precision oncology and clinical development of pan-RAS inhibitors, such as RMC-6236, for patients with these driver mutations in order to fully realize the potential benefit of RAS-targeted therapies.
KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • NRG1 (Neuregulin 1) • SPRY2 (Sprouty RTK Signaling Antagonist 2)
|
KRAS mutation • NRAS mutation • RAS mutation • HRAS mutation • NRG1 fusion • NRG1 mutation • NRG1 fusion
|
MSK-IMPACT
|
Mektovi (binimetinib) • pictilisib (GDC-0941) • ulixertinib (BVD-523) • SCH772984 • daraxonrasib (RMC-6236)
11ms
Afatinib in Advanced NRG1-Rearranged Malignancies (clinicaltrials.gov)
P2, N=3, Completed, German Cancer Research Center | Active, not recruiting --> Completed | N=60 --> 3 | Trial completion date: Dec 2024 --> Oct 2023 | Trial primary completion date: Dec 2024 --> Oct 2023
Trial completion • Enrollment change • Trial completion date • Trial primary completion date • Metastases
|
NRG1 (Neuregulin 1)
|
NRG1 fusion • NRG1 rearrangement • NRG1 fusion
|
Gilotrif (afatinib)
12ms
Pancreatic cancer biomarkers: A pathway to advance in personalized treatment selection. (PubMed, Cancer Treat Rev)
Consequently, there has been a growing interest in biomarkers that may help guide targeted therapy in pancreatic cancer. Therefore, this review aims to offer an updated perspective on biomarkers with therapeutic potential in pancreatic cancer.
Review • Journal • Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker • PARP Biomarker • IO biomarker
|
KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • NRG1 (Neuregulin 1) • PALB2 (Partner and localizer of BRCA2) • NTRK (Neurotrophic receptor tyrosine kinase)
|
KRAS mutation • MSI-H/dMMR • KRAS G12C • PALB2 mutation • NRG1 fusion • KRAS G12
1year
Expert Consensus on the Diagnosis and Treatment of NRG1/2 Gene Fusion Solid Tumors. (PubMed, Glob Med Genet)
Common treatment approaches involve pan-ERBB inhibitors, small molecule inhibitors targeting ERBB2 or ERBB3, and monoclonal antibodies. Given the current landscape of NRG1 and NRG2 in solid tumors, a consensus among diagnostic and treatment experts is proposed, and clinical trials hold promise for benefiting more patients with NRG1 and NRG2 gene fusion solid tumors.
Review • Journal
|
HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1) • CD74 (CD74 Molecule) • SLC3A2 (Solute Carrier Family 3 Member 2) • EGF (Epidermal growth factor) • NRG2 (Neuregulin 2)
|
NRG1 fusion • NRG1 fusion
1year
Neuregulin-1 and ALS19 (ERBB4): at the crossroads of amyotrophic lateral sclerosis and cancer. (PubMed, BMC Med)
Common signaling cascades between cancer and ALS may represent novel therapeutic targets for both diseases.
Review • Journal
|
EGFR (Epidermal growth factor receptor) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1) • ERBB4 (erb-b2 receptor tyrosine kinase 4)
|
NRG1 fusion • NRG1 fusion
1year
Fusion genes in pancreatic tumors. (PubMed, Trends Cancer)
Although they are rare, the therapeutic and diagnostic importance of these genomic events should not be underestimated, highlighting the need for quality-ensured molecular diagnostics in the management of cancer. Herein we review the existing literature on the role of fusion genes in pancreatic tumors and their clinical potential as effective biomarkers and therapeutic targets.
Review • Journal
|
KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • FGFR2 (Fibroblast growth factor receptor 2) • NRG1 (Neuregulin 1) • NTRK (Neurotrophic receptor tyrosine kinase) • PRKACA (Protein Kinase CAMP-Activated Catalytic Subunit Alpha)
|
KRAS wild-type • FGFR2 fusion • ALK fusion • RAS wild-type • NRG1 fusion • BRAF fusion
1year
Clinicopathologic and Genomic Characterization of High-Grade Invasive Solid Papillary Carcinoma of the Breast (USCAP 2024)
High-grade SPC are occasionally encountered and not well-characterized. Similar to their lower-grade counterparts, approximately half show NE differentiation. However, in contrast, these cases frequently have more aggressive features such as necrosis, LVI/nodal metastases and alterations in cellular proliferation pathways and tumor suppressor transcription factors.
Clinical • Tumor mutational burden
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • NRG1 (Neuregulin 1) • MLH1 (MutL homolog 1) • KMT2C (Lysine Methyltransferase 2C) • GATA3 (GATA binding protein 3) • SYP (Synaptophysin) • INSM1 (INSM Transcriptional Repressor 1)
|
PIK3CA mutation • NRG1 fusion • NRG1 mutation • NRG1 fusion
|
Tempus xT Assay • Oncotype DX Breast Recurrence Score®Test
1year
Clinicopathologic and Genomic Characterization of High-Grade Invasive Solid Papillary Carcinoma of the Breast (USCAP 2024)
High-grade SPC are occasionally encountered and not well-characterized. Similar to their lower-grade counterparts, approximately half show NE differentiation. However, in contrast, these cases frequently have more aggressive features such as necrosis, LVI/nodal metastases and alterations in cellular proliferation pathways and tumor suppressor transcription factors.
Clinical • Tumor mutational burden
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • NRG1 (Neuregulin 1) • MLH1 (MutL homolog 1) • KMT2C (Lysine Methyltransferase 2C) • GATA3 (GATA binding protein 3) • SYP (Synaptophysin) • INSM1 (INSM Transcriptional Repressor 1)
|
PIK3CA mutation • NRG1 fusion • NRG1 mutation • NRG1 fusion
|
Tempus xT Assay • Oncotype DX Breast Recurrence Score®Test
1year
The phase I/II eNRGy trial: Zenocutuzumab in patients with cancers harboring NRG1 gene fusions. (PubMed, Future Oncol)
Zenocutuzumab is a novel, bispecific IgG1 antibody that targets both HER2 and HER3 proteins and inhibits NRG1 binding through a 'Dock & Block®' mechanism of action. Here, we describe the rationale and design of the phase II component of the eNRGy trial, part of the overall, open-label phase I/II, multicenter trial exploring the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and antitumor activity of zenocutuzumab in patients with NRG1+ NSCLC, PDAC or other solid tumors.
P1/2 data • Review • Journal
|
HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1)
|
NRG1 fusion • NRG1 fusion
|
Bizengri (zenocutuzumab-zbco)
1year
Clinical findings and genomic characterization of NRG-1 alterations with a comprehensive genome profiling (CGP) in advanced non-small cell lung cancer (ANSCLC) (ELCC 2024)
Conclusions In our cohort, NRG-1 alterations resulted frequently associated with poor prognosis and main oncogene alterations and/or loss of function of oncosuppressor genes. Further investigations are needed.
Clinical • BRCA Biomarker • Metastases
|
KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • NRG1 (Neuregulin 1) • BRCA (Breast cancer early onset)
|
TP53 mutation • NRG1 fusion
|
TruSight Oncology 500 Assay
1year
A Study of Zenocutuzumab (MCLA-128) in Patients With Solid Tumors Harboring an NRG1 Fusion (eNRGy) (clinicaltrials.gov)
P2, N=250, Recruiting, Merus N.V. | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2022 --> Dec 2026
Trial completion date • Trial primary completion date
|
NRG1 (Neuregulin 1)
|
NRG1 fusion • NRG1 fusion
|
Bizengri (zenocutuzumab-zbco)
1year
Real-world outcomes associated with afatinib use in patients with solid tumors harboring NRG1 gene fusions. (PubMed, Lung Cancer)
This study provides real-world data on the characteristics of patients with NRG1 fusion-positive solid tumors treated with afatinib or other therapies; durable responses were observed in both groups. However, there were imbalances between the cohorts, and the study was not designed to compare outcomes. Further prospective/retrospective trials are required.
Journal • Real-world evidence • Real-world
|
NRG1 (Neuregulin 1)
|
NRG1 fusion • NRG1 fusion
|
Gilotrif (afatinib)
1year
Fluorescent in situ hybridization has limitations in screening NRG1 gene rearrangements. (PubMed, Diagn Pathol)
Considering the high cost of NGS, FISH remains a useful method for screening NRG1 fusions in various types of tumors. This study provides valuable insights into the molecular mechanisms of NRG1 fusion and identifies potential treatment targets for patients suffering from this disease.
Journal
|
ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1)
|
ERBB3 expression • NRG1 fusion • ERBB3 positive • NRG1 rearrangement • NRG1 fusion
1year
Trial completion date • Trial primary completion date
|
NRG1 (Neuregulin 1)
|
NRG1 fusion
|
Gilotrif (afatinib) • Xtandi (enzalutamide) • abiraterone acetate • Bizengri (zenocutuzumab-zbco)
over1year
Phase classification • Metastases
|
ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1) • EGF (Epidermal growth factor)
|
NRG1 fusion • ERBB3 mutation
|
gemcitabine • docetaxel • albumin-bound paclitaxel • HMBD-001
over1year
Analysis of CD74 Occurrence in Oncogenic Fusion Proteins. (PubMed, Int J Mol Sci)
Fusion proteins known to be oncogenic drivers, including those of CD74, are typically detected and targeted after standard chemotherapeutic plans fail and the disease relapses. The analysis reported herein provides insights into the early intervention of CD74 fusions and highlights the need for improved routine assessment methods so that targeted therapies can be applied while they are most effective.
Review • Journal
|
ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NRG1 (Neuregulin 1) • CD74 (CD74 Molecule) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • NRG2 (Neuregulin 2)
|
NTRK1 fusion • NRG1 fusion
over1year
Multiomic Characterization Reveals a Distinct Molecular Landscape in Young-Onset Pancreatic Cancer. (PubMed, JCO Precis Oncol)
In this large, real-world multiomic characterization of age-stratified molecular differences in pancreatic ductal adenocarcinoma, YOPC is associated with a distinct molecular landscape that has prognostic and therapeutic implications.
Journal • BRCA Biomarker • MSi-H Biomarker
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NRG1 (Neuregulin 1) • CD8 (cluster of differentiation 8) • SF3B1 (Splicing Factor 3b Subunit 1) • PALB2 (Partner and localizer of BRCA2) • RNF43 (Ring Finger Protein 43) • SMAD4 (SMAD family member 4) • HLA-DPA1 (Major Histocompatibility Complex, Class II, DP Alpha 1)
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TP53 mutation • BRCA2 mutation • MSI-H/dMMR • PALB2 mutation • KRAS wild-type • RAS wild-type • CDKN2A mutation • MET mutation • NRG1 fusion • BRAF fusion • RNF43 mutation • MET fusion
over1year
Multi-omic Characterization and Molecular Profiling of NUT Carcinoma (AMP 2023)
NRG1 fusion events are infrequently observed in ovarian, fallopian tube, and primary peritoneal carcinomas, and include a diversity of previously unknown partner genes. However, they may carry diagnostic significance in the context of borderline/low-grade serous tumors and have important therapeutic implications with the emergence of new targeted treatments.
Tumor mutational burden • BRCA Biomarker
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • PTEN (Phosphatase and tensin homolog) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • FGFR3 (Fibroblast growth factor receptor 3) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • ARID1A (AT-rich interaction domain 1A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NRG1 (Neuregulin 1) • KMT2D (Lysine Methyltransferase 2D) • CDK12 (Cyclin dependent kinase 12) • MUC16 (Mucin 16, Cell Surface Associated) • NOTCH2 (Notch 2) • CHEK2 (Checkpoint kinase 2) • ADAM9 (ADAM Metallopeptidase Domain 9) • EP300 (E1A binding protein p300) • RAD51D (RAD51 paralog D) • WRN (WRN RecQ Like Helicase) • IR (Insulin receptor) • FANCE (FA Complementation Group E) • JAG1 (Jagged Canonical Notch Ligand 1) • CXADR (CXADR Ig-Like Cell Adhesion Molecule) • FANCC (FA Complementation Group C) • TMEM65 (Transmembrane Protein 65) • TNFRSF12A (TNF Receptor Superfamily Member 12A)
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NRG1 fusion • NRG1 fusion
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MI Tumor Seek™
over1year
Analytical Validation (Accuracy, Reproducibility, Limit of Detection) of Foundation One RNA Assay For Fusion Detection In 189 Clinical Tumor Specimens (AMP 2023)
F1R assay successfully detected oncogenic fusions with high concordance to orthogonal NGS-based tests. This study demonstrated the robustness of F1R and supports its use as a supplement to tissue DNA CGP in routine clinical practice. Additional work is required to clarify optimal clinical scenarios for fusion detection and enable GEP biomarkers for clinical use.
Clinical
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BRAF (B-raf proto-oncogene) • FGFR3 (Fibroblast growth factor receptor 3) • NRG1 (Neuregulin 1)
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NRG1 fusion • BRAF fusion • FGFR3 fusion • NRG1 fusion
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FoundationOne®RNA
over1year
Detection of NRG1 Fusion Events in Ovarian, Fallopian Tube, and Primary Peritoneal Carcinomas (AMP 2023)
This large patient cohort demonstrates that NC is characterized by NUTM1 gene fusions, low mutational burden, and general lack of additional oncogenic drivers. The prognosis of NCs remains dismal, and future work could focus on subpopulations of immune cell-rich tumors that might be responsive to immunotherapy.
Tumor mutational burden • IO biomarker
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TMB (Tumor Mutational Burden) • NRG1 (Neuregulin 1) • KMT2D (Lysine Methyltransferase 2D) • KMT2C (Lysine Methyltransferase 2C) • KDM6A (Lysine Demethylase 6A) • NSD3 (Nuclear Receptor Binding SET Domain Protein 3) • BRD4 (Bromodomain Containing 4) • NUTM1 (NUT Midline Carcinoma Family Member 1) • BRD3 (Bromodomain Containing 3)
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TMB-L • NRG1 fusion • NRG1 fusion
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MI Tumor Seek™
over1year
Pulmonary invasive mucinous adenocarcinoma. (PubMed, Histopathology)
Accordingly, these unique features require different therapeutic approaches when compared to nonmucinous adenocarcinomas in general. In this article, we review recent updates on the histopathological, clinical, and molecular features of IMAs, and also highlight some unresolved issues for future studies.
Review • Journal
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HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • NRG1 (Neuregulin 1)
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KRAS mutation • NRG1 fusion • HER-2 fusion