A5005400331- HER2/EGFR in Cancer Research
- Cancer Cells and Metastasis
- Cancer-related gene regulation
- Monoclonal and Polyclonal Antibodies Research
- Wnt/β-catenin signaling in development and cancer
- Cytokine Signaling Pathways and Interactions
- Glycosylation and Glycoproteins Research
- Cell Adhesion Molecules Research
- Estrogen and related hormone effects
- Kruppel-like factors research
- Cancer Immunotherapy and Biomarkers
- Cancer Genomics and Diagnostics
- Lung Cancer Treatments and Mutations
- Advanced biosensing and bioanalysis techniques
- Single-cell and spatial transcriptomics
- Lymphoma Diagnosis and Treatment
- Fibroblast Growth Factor Research
- Peptidase Inhibition and Analysis
- Advanced Biosensing Techniques and Applications
- Biochemical and Molecular Research
- Advanced Fluorescence Microscopy Techniques
- Immune Cell Function and Interaction
- Microtubule and mitosis dynamics
- T-cell and B-cell Immunology
- Melanoma and MAPK Pathways
Genmab (Netherlands)
2024
Merus (Netherlands)
2021-2022
Harvard University
2016-2022
University Medical Center Utrecht
2010-2015
The Netherlands Cancer Institute
2013
Utrecht University
2013
Abstract Recently, organoid technology has been used to generate a large repository of breast cancer organoids. Here we present an extensive evaluation the ability culture preserve complex stem/progenitor and differentiated cell types via long-term propagation normal human mammary tissues. Basal/stem luminal progenitor cells can differentiate in mature basal types, including ER+ that have challenging maintain culture. Cells associated with increased risk also be propagated. Single-cell...
Abstract NRG1 rearrangements are recurrent oncogenic drivers in solid tumors. binds to HER3, leading heterodimerization with other HER/ERBB kinases, increased downstream signaling, and tumorigenesis. Targeting ERBBs, therefore, represents a therapeutic strategy for these cancers. We investigated zenocutuzumab (Zeno; MCLA-128), an antibody-dependent cellular cytotoxicity–enhanced anti-HER2xHER3 bispecific antibody, fusion–positive isogenic patient-derived cell lines xenograft models. Zeno...
To decipher the molecular mechanisms of biological function, it is critical to map composition individual cells or even more importantly tissue samples in context their environment situ. Immunofluorescence (IF) provides specific labeling for profiling. However, conventional IF methods have finite multiplexing capabilities due spectral overlap fluorophores. Various sequential imaging been developed circumvent this limit but are not widely adopted common limitation requiring multirounds slow...
Metastatic breast cancer is the major cause of cancer-related death among women in Western world. Invasive carcinoma cells are able to counteract apoptotic signals absence anchorage, enabling cell survival during invasion and dissemination. Although loss E-cadherin a cardinal event development progression invasive lobular (ILC), little known about underlying mechanisms that govern these processes. Using mouse model human ILC, we show here cytosolic p120-catenin (p120) regulates tumor growth...
YAP has a nontranscriptional role in the separation of daughter cells during mitosis.
Metastatic breast cancer remains the chief cause of cancer-related death among women in Western world. Although loss cell-cell adhesion is key to progression, little known about underlying mechanisms that drive tumor invasion and metastasis. Here, we show somatic p120-catenin (p120) a conditional mouse model noninvasive mammary carcinoma results formation stromal-dense tumors resemble human metaplastic metastasize lungs lymph nodes. Loss p120 anchorage-dependent cell lines strongly promoted...
Abstract E-cadherin inactivation underpins the progression of invasive lobular breast carcinoma (ILC). In ILC, p120-catenin (p120) translocates to cytosol where it controls anchorage independence through Rho-Rock signaling pathway, a key mechanism driving tumor growth and metastasis. We now demonstrate that anchorage-independent ILC cells show an increase in nuclear p120, which results relief transcriptional repression by Kaiso. To identify Kaiso target genes control we performed genome-wide...
Abstract Neuregulin 1 (NRG1) is a ligand that binds to HER3, promotes HER2/HER3 dimerization and PI3K/AKT/mTOR signaling, causes malignant transformation. Zenocutuzumab (Zeno, MCLA-128) humanized IgG1 bispecific antibody docks on HER2, preventing heterodimerization with while also blocking NRG1 interaction potently inhibiting NRG1-induced HER2:HER3 proliferation survival signaling of cancer cells. High expression arising from autocrine or gene amplification associated poor prognosis in...
Abstract To decipher the molecular mechanism of biological function, it is critical to map composition individual cells in context their environment situ . Immunofluorescence (IF) provides specific labeling for profiling. However, conventional IF methods have finite multiplexing capabilities due spectral overlap fluorophores. Various sequential imaging been developed circumvent this limit, but are not widely adopted common limitation requiring multi-rounds slow (typically over 2 hours at...
Abstract Neuregulin 1 (NRG1) fusion proteins are oncogenic drivers in multiple cancer types, including non-small cell lung cancer, pancreas adenocarcinoma, and other solid tumors. NRG1 bind to HER3 signal through HER2/HER3 heterodimers, leading transformation. Zenocutuzumab is an humanized IgG1 bispecific antibody that specifically potently blocks fusion-driven signaling of the heterodimeric complex. binds via its anti-HER2 monovalent Fab arm domain I HER2. Docking zenocutuzumab this...
Abstract Fusions involving the neuregulin 1 gene (NRG1) occur at low frequency in pancreatic, lung, and other cancers. NRG1 fusion oncoproteins bind to HER3, leading heterodimerization with HER2 potent activation of downstream signaling mainly via PI3K-AKT pathway. Zenocutuzumab (Zeno, MCLA-128), an ADCC-enhanced anti-HER2×HER3 bi-specific antibody, uniquely ‘docks' on HER2, position antibody subsequently ‘block' from interacting effectively preventing HER2:HER3 signaling. Our goal this...
<p>PDF - 346K, Loss of p120 and subsequent AJ inactivation does not induce autocrine survival pathways or increased EGF binding.</p>
<p>PDF - 4445K, Comparative immunohistochemistry in human and mouse breast cancer.</p>
<p>PDF - 174K, Loss of p120 does not affect Rho GTPase activity.</p>
<p>PDF - 828K, p120 knockout sensitizes tumor cells to growth factor signaling.</p>
<p>PDF - 4684K, p120 knockdown decreases AJ member expression levels and disrupts cell-cell contact in breast cancer cells.</p>