A5057368899- Cancer, Hypoxia, and Metabolism
- Cancer, Stress, Anesthesia, and Immune Response
- interferon and immune responses
- Cancer Research and Treatments
- Cancer Immunotherapy and Biomarkers
- Cancer-related Molecular Pathways
- Growth Hormone and Insulin-like Growth Factors
- Genetic factors in colorectal cancer
- Cytokine Signaling Pathways and Interactions
- DNA Repair Mechanisms
- Cell death mechanisms and regulation
- Phagocytosis and Immune Regulation
- Cancer Cells and Metastasis
- Immunotherapy and Immune Responses
- Nuclear Structure and Function
- Protein Degradation and Inhibitors
- Cellular Mechanics and Interactions
- Molecular Biology Techniques and Applications
- Microtubule and mitosis dynamics
- Gene expression and cancer classification
- Bioinformatics and Genomic Networks
- Machine Learning in Bioinformatics
- Cell Adhesion Molecules Research
- MicroRNA in disease regulation
- Hippo pathway signaling and YAP/TAZ
Boehringer Ingelheim (Austria)
2008-2023
Broad Institute
2021
Boehringer Ingelheim (Germany)
2007-2019
Research Institute of Molecular Pathology
2015
Institute of Molecular Biotechnology
2015
University of Vienna
1997
Abstract The ruthenium complex sodium trans-[tetrachloridobis(1H-indazole)ruthenate(iii)] (KP1339/IT-139) showed preclinical activity in a variety of vivo tumor models including highly predictive colon cancer model. compound has entered clinical trials, where patients experienced disease stabilization accompanied by mild side effects. KP1339, GRP78 inhibitor, disrupts endoplasmic reticulum (ER) homeostasis leading to cell death. PERK/eIF2α-branch the ER plays an essential role cascade events...
Targeted cancer therapy is based on exploiting selective dependencies of tumor cells. By leveraging recent functional screening data cell lines we identify Werner syndrome helicase (WRN) as a novel specific vulnerability microsatellite instability-high (MSI-H) MSI, caused by defective mismatch repair (MMR), occurs frequently in colorectal, endometrial and gastric cancers. We demonstrate that WRN inactivation selectively impairs the viability MSI-H but not stable (MSS) colorectal lines. In...
Plakophilin 3 (PKP3) belongs to the p120ctn family of armadillo‐related proteins predominantly functioning in desmosome formation. Here we report that PKP3 is transcriptionally repressed by E‐cadherin repressor ZEB1 metastatic cancer cells. physically associates with two conserved E‐box elements promoter and partially represses activity corresponding human mouse fragments reporter gene assays. In tumours upregulated invasive cells at tumour–host interface, which accompanied downregulation...
Polo-like kinase 1 (Plk1), a member of the family serine/threonine kinases, is key regulator multiple steps in mitosis. Here we report on pharmacological profile volasertib, potent and selective Plk inhibitor, preclinical models acute myeloid leukemia (AML) including established cell lines, bone marrow samples from AML patients short-term culture, subcutaneous as well disseminated vivo immune-deficient mice. Our results indicate that volasertib highly efficacious single agent combination...
Organometallic metal(arene) anticancer agents were believed to confer low selectivity for potential cellular targets. However, the ruthenium(arene) pyridinecarbothioamide (plecstatin-1) showed target plectin, a scaffold protein and cytolinker. We employed three-dimensional cancer spheroid model that plecstatin-1 limited growth, induced changes in morphology architecture of tumour spheroids by disrupting cytoskeletal organization. Additionally, we demonstrated oxidative stress, followed...
Emerging in vitro and vivo data underline the crucial role of G-protein-coupled receptors (GPCRs) tumorigenesis. Here, we report contribution hGPR87, a predicted member P2Y subfamily GPCRs, to proliferation survival human tumor cell lines. hGPR87 mRNA transcript was found be preferentially overexpressed squamous carcinomas (SCCs) different locations their lymph node metastases. Up-regulation both, protein, detected samples SCC lung, cervix, skin head neck (pharynx, larynx epiglottis). In...
We established co-cultures of invasive or non-invasive NSCLC cell lines and various types fibroblasts (FBs) to more precisely characterize the molecular mechanism tumor-stroma crosstalk in lung cancer. The HGF-MET-ERK1/2-CREB-axis was shown contribute onset phenotype Calu-1 with HGF being secreted by FBs. Differential expression analysis respective mono- revealed an upregulation NFκB-related genes exclusively Calu-1. Cytokine Array- ELISA-based characterization "cytokine fingerprints"...
Clinical studies of pharmacologic agents targeting the insulin-like growth factor (IGF) pathway in unselected cancer patients have so far demonstrated modest efficacy outcomes, with objective responses being rare. As such, identification selection biomarkers for enrichment potential responders represents a high priority future trials these agents. Several reports described IGF2 expression subset colorectal cancers, focal amplification responsible some cases. We defined novel cut-off value...
Activation of TRAILR2 has emerged as an important therapeutic concept in cancer treatment. agonistic molecules have only had limited clinical success, to date, due either lack efficacy or hepatotoxicity. BI 905711 is a novel tetravalent bispecific antibody targeting both and CDH17 represents liver-sparing agonist specifically designed overcome the disadvantages previous strategies. Here, we show that effectively triggered apoptosis broad panel CDH17-positive colorectal tumor cells vitro....
Scp160p ( Saccharomyces cerevisiae protein involved in the control of ploidy), a polypeptide with molecular mass around 160 kDa, is associated nuclear envelope and endoplasmic reticulum. The most noteworthy phenotype SCP160 deletion mutants decrease viability an increased number chromosomes surviving cells [Wintersberger, U., Kühne, C. & Karwan, A. (1995) Yeast 11 , 929–944]. contains 14 KH domains, conserved motifs that have lately been identified variety RNA‐binding proteins. In this...
Ordino is a web-based analysis tool for cancer genomics that allows users to flexibly rank, filter and explore genes, cell lines tissue samples based on pre-loaded data, including The Cancer Genome Atlas, the Cell Line Encyclopedia manually uploaded information. Interactive tabular data visualization facilitates user-driven prioritization process forms core component of Ordino. Detail views selected items complement exploration. Findings can be stored, shared reproduced via integrated...
Abstract MDM2 inhibitors block the interaction between Tumor Protein p53 (TP53) and MDM2, its key negative regulator, represent a new therapeutic concept for cancer therapy. are designed to restore activity in TP53 wild-type tumors. Several currently being evaluated early clinical development with mainly daily dosing regimens. However, recent data suggest myelosuppression as an on-target, dose-limiting toxicity this class of inhibitors. Particularly thrombocytopenia could limit utility Hence...
Oncogenic mutations in the small GTPase Ras contribute to ~30% of human cancers. However, alone are insufficient for tumorigenesis, therefore it is paramount identify cooperating cancer-relevant signaling pathways. We devised an vivo near genome-wide, functional screen Drosophila and discovered multiple novel, evolutionarily-conserved pathways controlling Ras-driven epithelial tumorigenesis. Human gene orthologs fly hits were significantly downregulated thousands primary tumors, revealing...
Abstract MDM2 inhibitors block the interaction between Tumor Protein p53 (TP53) and MDM2, its key negative regulator, represent a new therapeutic concept in cancer therapy. are designed to restore activity TP53 wild-type tumors. Several currently being evaluated early clinical development. While tumor targeting of has been well documented, recent preclinical data with tool compound Nutlin-3 have shown that activation by local, intra-tumoral injections induces anti-tumor immunity (Cancer Res...
// David J. Lamb 1 , Aleksander Rust 2 Albin Rudisch 3 Tobias Glüxam 4 Nathalie Harrer Herwig Machat Ingrid Christ Florian Colbatzky 5 Andreas Wernitznig Annika Osswald 6 and Wolfgang Sommergruber 7 Immunology & Respiratory, Boehringer Ingelheim Pharma GmbH Co. KG, 88397 Biberach an der Riß, Germany Cancer Biology Genetics Program, Memorial Sloan Kettering Center, New York, NY 10065, USA Cell Signalling, RCV Co A-1121 Vienna, Austria Department of Medicine I, Comprehensive Medical University...
Abstract Summary Ordino is a web-based analysis tool for cancer genomics that allows users to flexibly rank, filter, and explore genes, cell lines, tissue samples based on pre-loaded data, including The Cancer Genome Atlas (TCGA), the Cell Line Encyclopedia (CCLE), manually uploaded information. Interactive tabular data visualization facilitates user-driven prioritization process forms core component of Ordino. Detail views selected items complement exploration. Findings can be stored,...
Abstract MDM2 inhibitors block the interaction between Tumor Protein p53 (TP53) and MDM2, its key negative regulator, represent a new therapeutic concept for cancer therapy. are designed to restore activity in TP53 wild-type tumors. Several currently being evaluated early clinical development with mainly daily dosing regimens. However, recent data suggest myelosuppression as an on-target, dose-limiting toxicity this class of inhibitors. Particularly, thrombocytopenia could limit utility...
Abstract MDM2-p53 antagonists block the interaction between Tumor Protein p53 and MDM2, its key negative regulator, represent a new therapeutic concept for cancer therapy. are designed to restore activity in TP53 wild-type tumors. Several currently being evaluated early clinical development. BI-907828 is novel potent antagonist with optimized drug-like properties that has shown efficacy human tumor xenograft models at daily low oral dose as well intermittent high schedules. Recent...
Abstract The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has the capability to induce apoptosis in a wide variety of cells and emerged as an important therapeutic concept for cancer treatment. To date however, TRAILR2 agonistic antibodies, designed trigger cell apoptosis, have only had limited clinical success due either lack efficacy or liver toxicity. BI 905711, tetravalent bispecific antibody targeting both CDH17, was overcome disadvantages current antibodies....
Abstract Cancer cell lines are important models for drug tests and viability screens. For the evaluation understanding of differences between two groups lines, we created a research software application called CLIFF (cell line differences). finds in mutational pattern or DNA copy number, lists visualizes significantly differentially expressed genes proteins performs Gene Set Enrichment Analysis (GSEA) to name few. Today have data from large panels cancer consisting gene-, protein- microRNA...