News - CD74-NRG1 fusion

almost2years

Liquid biopsy-based comprehensive genomic proﬁling reveal mutational landscape in real-world patients with unresectable NSCLC (AACR 2023)

"This study revealed the comprehensive mutational landscape of advanced NSCLC through liquid biopsy, providing novel biomarkers for clinical diagnosis and targeted therapy mechanism studies."

almost 2 years ago

Real-world evidence • Clinical • Liquid biopsy

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • RET (Ret Proto-Oncogene) • PTEN (Phosphatase and tensin homolog) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • EML4 (EMAP Like 4) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • NRG1 (Neuregulin 1) • KIF5B (Kinesin Family Member 5B) • CD74 (CD74 Molecule) • ETV6 (ETS Variant Transcription Factor 6) • NCOA4 (Nuclear Receptor Coactivator 4) • NTRK (Neurotrophic receptor tyrosine kinase)

NTRK1 fusion • RET fusion • EML4-ALK fusion • ALK fusion • KIF5B-RET fusion • ETV6-NTRK3 fusion • NRG1 fusion • NCOA4-RET fusion • CD74-NRG1 fusion • NRG1 fusion • NTRK fusion

PredicineCARE™

almost3years

CD74-NRG1 fusions are oncogenic in vivo and induce therapeutically tractable ERBB2:ERBB3 heterodimerization. (PubMed, Mol Cancer Ther)

Thus, NRG1 gene fusions are recurrent driver oncogenes that cause oncogene dependency. Consistent with these findings, patients with NRG1 fusion-positive cancers respond to therapy targeting the ERBB2:ERBB3 receptors.

almost 3 years ago

Preclinical • 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)

NRG1 fusion • CD74-NRG1 fusion • CD74 expression • NRG1 fusion

over3years

The anti-HER3 monoclonal antibody seribantumab effectively inhibits growth of patient-derived and isogenic cell line and xenograft models with oncogenic NRG1 fusions. (PubMed, Clin Cancer Res)

Seribantumab treatment blocked activation of the four ERBB family members and of downstream signaling, leading to inhibition of NRG1 fusion-dependent tumorigenesis in vitro and in vivo in breast, lung and ovarian patient-derived cancer models.

over 3 years ago

Preclinical • Journal

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • NRG1 (Neuregulin 1) • CCND1 (Cyclin D1) • CD74 (CD74 Molecule) • SLC3A2 (Solute Carrier Family 3 Member 2)

NRG1 fusion • SLC3A2-NRG1 fusion • CCND1 expression • CD74-NRG1 fusion • TP53 expression • CD74 expression

Gilotrif (afatinib) • seribantumab (MM-121)

over3years

Comprehensive analysis of the clinicopathological features, targetable profile, and prognosis of mucinous adenocarcinoma of the lung. (PubMed, J Cancer Res Clin Oncol)

Mucinous adenocarcinoma had a low frequency of targetable genetic variants and PD-L1 immunoreactivity; however, KRAS mutations were frequent. Pneumonic appearance on CT imaging and KRAS mutations were clinicopathological features associated with a worse prognosis.

over 3 years ago

Clinical • Journal • PD(L)-1 Biomarker • IO biomarker

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRG1 (Neuregulin 1) • CD74 (CD74 Molecule) • NKX2-1 (NK2 Homeobox 1)

PD-L1 expression • KRAS mutation • EGFR mutation • BRAF mutation • NRG1 fusion • CD74-NRG1 fusion • EGFR fusion • NKX2-1 expression

over4years

[VIRTUAL] Landscape of targetable alterations discovered by next generation sequencing demonstrates the role a community hospital can play in precision-guided oncology: Experience from Lenox Hill Hospital. (ASCO 2020)

Four samples harbored crizotinib-sensitive mutations (2 MET amplifications and 2 MET exon 14 skipping mutations)... We identified 92/511 samples (18%) with clinically actionable mutations; distributed in 32% early stage and 18% advanced stage disease, indicating that actionable mutations are present at an increased frequency in early stage solid malignancies in our data set and trials to investigate targeted therapy in such settings should be considered. Furthermore, we show that a community-based hospital can be a site for future clinical trials of small molecule inhibitors and bring precision-guided medicine to additional patients. Research Funding: None

over 4 years ago

Clinical • Next-generation sequencing

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • FGFR3 (Fibroblast growth factor receptor 3) • NRG1 (Neuregulin 1) • CD74 (CD74 Molecule)

TP53 mutation • BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • BRAF V600 • MET amplification • MET exon 14 mutation • FGFR3 mutation • NRG1 fusion • CD74-NRG1 fusion • BRAF mutation + MET amplification • FGFR3 amplification

Xalkori (crizotinib)