A5007350056- DNA Repair Mechanisms
- PARP inhibition in cancer therapy
- CRISPR and Genetic Engineering
- BRCA gene mutations in cancer
- Epigenetics and DNA Methylation
- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Cancer Genomics and Diagnostics
- Advanced biosensing and bioanalysis techniques
- PI3K/AKT/mTOR signaling in cancer
- Cancer-related gene regulation
- Cancer-related Molecular Pathways
- RNA modifications and cancer
- Electrochemical Analysis and Applications
- Innovative Microfluidic and Catalytic Techniques Innovation
- Cancer Cells and Metastasis
- 3D Printing in Biomedical Research
- Cytokine Signaling Pathways and Interactions
- Lung Cancer Research Studies
- Cancer therapeutics and mechanisms
- Microfluidic and Bio-sensing Technologies
- Fibroblast Growth Factor Research
- Carcinogens and Genotoxicity Assessment
- Mitochondrial Function and Pathology
- Cancer Research and Treatments
The Netherlands Cancer Institute
2016-2025
Oncode Institute
1996-2024
Erasmus MC Cancer Institute
2016-2021
Cancer Genomics Centre
2009-2016
Parnassia Groep
2016
Erasmus University Rotterdam
2006-2014
Erasmus MC
2006-2014
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...
Abstract The limited efficacy of immune checkpoint inhibitor treatment in triple-negative breast cancer (TNBC) patients is attributed to sparse or unresponsive tumor-infiltrating lymphocytes, but the mechanisms that lead a therapy resistant tumor microenvironment are incompletely known. Here we show strong correlation between MYC expression and loss signatures human TNBC. In mouse models TNBC proficient deficient type 1 susceptibility gene (BRCA1), overexpression dramatically decreases...
Summary Dietary restriction (DR) extends lifespan and increases resistance to multiple forms of stress, including ischemia reperfusion injury the brain heart in rodents. While maximal effects on require long‐term restriction, kinetics onset benefits against acute stress is not known. Here, we show that 2–4 weeks 30% DR improved survival kidney function following renal mice. Brief periods water‐only fasting were similarly effective at protecting ischemic damage. Significant protection...
Selective elimination of BRCA1-deficient cells by inhibitors poly(ADP-ribose) polymerase (PARP) is a prime example the concept synthetic lethality in cancer therapy. This interaction counteracted restoration BRCA1-independent homologous recombination through loss factors such as 53BP1, RIF1, and REV7/MAD2L2, which inhibit end resection DNA double-strand breaks (DSBs). To identify additional involved this process, we performed CRISPR/SpCas9-based loss-of-function screens selected for that...
Large-scale sequencing studies are rapidly identifying putative oncogenic mutations in human tumors. However, discrimination between passenger and driver events tumorigenesis remains challenging requires vivo validation reliable animal models of cancer. In this study, we describe a novel strategy for candidate tumor suppressors implicated invasive lobular breast carcinoma (ILC), which is hallmarked by loss the cell-cell adhesion molecule E-cadherin. We an approach to model ILC intraductal...
Heterozygous germline mutations in breast cancer 1 (BRCA1) strongly predispose women to cancer. BRCA1 plays an important role DNA double-strand break (DSB) repair via homologous recombination (HR), which is for tumor suppression. Although BRCA1-deficient cells are highly sensitive treatment with DSB-inducing agents through their HR deficiency (HRD), BRCA1-associated tumors display heterogeneous responses platinum drugs and poly(ADP-ribose) polymerase (PARP) inhibitors clinical trials. It...
Abstract The cell adhesion glycoprotein E-cadherin (CDH1) is commonly inactivated in breast tumors. Precision medicine approaches that exploit this characteristic are not available. Using perturbation screens tumor cells with CRISPR/Cas9-engineered CDH1 mutations, we identified synthetic lethality between deficiency and inhibition of the tyrosine kinase ROS1. Data from large-scale genetic molecularly diverse lines established E-cadherin/ROS1 was only robust face considerable molecular...
Abstract Somatic hotspot mutations and structural amplifications fusions that affect fibroblast growth factor receptor 2 (encoded by FGFR2 ) occur in multiple types of cancer 1 . However, clinical responses to FGFR inhibitors have remained variable 1–9 , emphasizing the need better understand which alterations are oncogenic therapeutically targetable. Here we apply transposon-based screening 10,11 tumour modelling mice 12,13 find truncation exon 18 (E18) Fgfr2 is a potent driver mutation....
Patient-derived organoids (PDOs) are widely heralded as a drug-screening platform to develop new anti-cancer therapies. Here, we use drug-repurposing library screen PDOs of colorectal cancer (CRC) identify hidden vulnerabilities within therapy-induced phenotypes. Using microscopy-based that accurately scores drug-induced cell killing, have tested 414 putative drugs for their ability switch the EGFRi/MEKi-induced cytostatic phenotype toward cytotoxicity. A majority validated hits (9/37)...
BRCA1 and BRCA2 both function in DNA double-strand break repair by homologous recombination (HR). Due to their HR defect, BRCA1/2-deficient cancers are sensitive poly(ADP-ribose) polymerase inhibitors (PARPis), but they eventually acquire resistance. Preclinical studies yielded several PARPi resistance mechanisms that do not involve BRCA1/2 reactivation, relevance the clinic remains elusive. To investigate which BRCA1/2-independent drive spontaneous vivo, we combine molecular profiling with...
Article16 September 2019Open Access Transparent process SLC1A3 contributes to L-asparaginase resistance in solid tumors Jianhui Sun Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Amsterdam, Department Genetics, Erasmus University Medical Center, Rotterdam, Search for more papers by this author Remco Nagel Esther A Zaal Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center Research, Utrecht University, Utrecht, Alejandro Piñeiro Ugalde Ruiqi Han Natalie Proost...
Currently, all soft tissue sarcomas (STS) are irradiated by the same regimen, disregarding possible subtype-specific radiosensitivities. To gain further insight, cellular radiosensitivity was investigated in a panel of sarcoma cell lines. Fourteen lines, derived from synovial sarcoma, leiomyosarcoma, fibrosarcoma and liposarcoma origin, were submitted to clonogenic survival assays. Cells with single doses 1-8 Gy surviving fraction (SF) calculated resulting response data. Alpha/beta (α/β)...
Over 90% of pancreatic cancers present mutations in KRAS, one the most common oncogenic drivers overall. Currently, KRAS mutant isoforms cannot be targeted directly. Moreover, targeting single RAS downstream effectors induces adaptive resistance mechanisms. We report here on combined inhibition SHP2, upstream using allosteric inhibitor RMC-4550 and ERK, LY3214996. This combination shows synergistic anti-cancer activity vitro, superior disruption MAPK pathway, increased apoptosis induction...
Abstract The defect in homologous recombination (HR) found BRCA1-associated cancers can be therapeutically exploited by treatment with DNA-damaging agents and PARP inhibitors. We others previously reported that BRCA1-deficient tumors are initially hypersensitive to the inhibition of topoisomerase I/II PARP, but acquire drug resistance through restoration HR activity loss end-resection antagonists 53BP1/RIF1/REV7/Shieldin/CST pathway. Here, we identify radiotherapy as an acquired...
Malignant rhabdoid tumors (MRTs) represent one of the most aggressive childhood malignancies. No effective treatment options are available, and prognosis is, therefore, dismal. Previous studies have demonstrated that tumor organoids capture heterogeneity patient can be used to predict response therapy. Here, we perform drug screening on patient-derived normal identify MRT-specific therapeutic vulnerabilities. We neddylation inhibitor MLN4924 as a potential agent. Mechanistically, find...