A5061340130- PARP inhibition in cancer therapy
- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- Cancer Genomics and Diagnostics
- BRCA gene mutations in cancer
- Cancer Cells and Metastasis
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Cancer Research and Treatments
- Genomics and Chromatin Dynamics
- Fibroblast Growth Factor Research
- Cancer-related gene regulation
- Wnt/β-catenin signaling in development and cancer
- Nutrition, Genetics, and Disease
- Animal Genetics and Reproduction
- Molecular Biology Techniques and Applications
- Cytokine Signaling Pathways and Interactions
- Gene expression and cancer classification
- HER2/EGFR in Cancer Research
- Metastasis and carcinoma case studies
- Lung Cancer Treatments and Mutations
- Cancer Immunotherapy and Biomarkers
- Bioinformatics and Genomic Networks
- Cancer therapeutics and mechanisms
Oncode Institute
2016-2025
The Netherlands Cancer Institute
2016-2025
Erasmus MC
2012-2023
Erasmus MC Cancer Institute
2012-2023
Molecular Biology Consortium
2023
Cancer Genomics Centre
2010-2021
Essen University Hospital
2021
University Hospital Cologne
2019-2021
Johns Hopkins University
2020
Universidade de Vigo
2020
Whereas target-specific drugs are available for treating ERBB2-overexpressing and hormone receptor-positive breast cancers, no tailored therapy exists receptor- ERBB2-negative ("triple-negative") mammary carcinomas. Triple-negative tumors account 15% of all cancers frequently harbor defects in DNA double-strand break repair through homologous recombination (HR), such as BRCA1 dysfunction. The DNA-repair characteristic BRCA1-deficient cells confer sensitivity to poly(ADP-ribose) polymerase 1...
Medulloblastomas are among the most common malignancies in childhood, and they associated with substantial mortality morbidity. The molecular pathogenesis as well ontogeny of these neoplasms is still poorly understood. We have generated a mouse model for medulloblastoma by Cre–LoxP -mediated inactivation Rb p53 tumor suppressor genes cerebellar external granular layer (EGL) cells. GFAP–Cre recombination was found both astrocytes immature precursor cells EGL developing cerebellum. GFAP–Cre;Rb...
Resource14 January 2019Open Access Transparent process Long-term expanding human airway organoids for disease modeling Norman Sachs Oncode Institute, Hubrecht Institute-KNAW and UMC Utrecht, The Netherlands Search more papers by this author Angelos Papaspyropoulos Domenique D Zomer-van Ommen Wilhelmina Children's Hospital Inha Heo Lena Böttinger Dymph Klay St. Antonius Nieuwegein, Fleur Weeber Cancer Amsterdam, Guizela Huelsz-Prince FOM Institute AMOLF, Nino Iakobachvili Maastricht...
The use of Cre/ loxP recombination in mammalian cells has expanded rapidly. We describe here that Cre expression cultured may result a markedly reduced proliferation and this effect is dependent on the endonuclease activity Cre. Chromosome analysis after revealed numerous chromosomal aberrations an increased number sister chromatid exchanges. Titration experiments mouse embryo fibroblasts with ligand-regulatable Cre-ER T show toxicity level activity. Prolonged, low levels permit without...
Combinatorial clinical trials of PARP inhibitors with immunotherapies are ongoing, yet the immunomodulatory effects inhibition have been incompletely studied. Here, we sought to dissect mechanisms underlying inhibitor-induced changes in tumor microenvironment BRCA1-deficient triple-negative breast cancer (TNBC). We demonstrate that inhibitor olaparib induces CD8+ T-cell infiltration and activation vivo, depletion severely compromises antitumor efficacy. Olaparib-induced recruitment is...
Autotaxin (ATX), or nucleotide pyrophosphatase-phosphodiesterase 2, is a secreted lysophospholipase D that promotes cell migration, metastasis, and angiogenesis. ATX generates lysophosphatidic acid (LPA), lipid mitogen motility factor acts on several G protein-coupled receptors. Here we report ATX-deficient mice die at embryonic day 9.5 (E9.5) with profound vascular defects in yolk sac embryo resembling the Galpha13 knockout phenotype. Furthermore, E8.5, embryos showed allantois...
Inhibition of PARP is a promising therapeutic strategy for homologous recombination-deficient tumors, such as BRCA1-associated cancers. We previously reported that BRCA1-deficient mouse mammary tumors may acquire resistance to the clinical inhibitor (PARPi) olaparib through activation P-glycoprotein drug efflux transporter. Here, we show tumor-specific genetic inactivation increases long-term response olaparib, but these eventually developed PARPi resistance. In fraction cases, this caused...
Women carrying germ-line mutations in BRCA1 are strongly predisposed to developing breast cancers with characteristic features also observed sporadic basal-like cancers. They appear as high-grade tumors high proliferation rates and pushing borders. On the molecular level, they negative for hormone receptors ERBB2, display frequent TP53 mutations, express basal epithelial markers. To study role of P53 loss function cancer development, we generated conditional mouse models tissue-specific...
BackgroundBRCA1 and BRCA2 (BRCA1/2)-deficient tumors display impaired homologous recombination repair (HRR) enhanced sensitivity to DNA damaging agents or poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi). Their efficacy in germline BRCA1/2 (gBRCA1/2)-mutated metastatic breast cancers has been recently confirmed clinical trials. Numerous mechanisms of PARPi resistance have described, whose relevance gBRCA-mutated cancer is unknown. This highlights the need identify functional biomarkers...