A5054841460- Neuroblastoma Research and Treatments
- Bioinformatics and Genomic Networks
- Cancer, Hypoxia, and Metabolism
- Colorectal Cancer Treatments and Studies
- Genetic factors in colorectal cancer
- Biomedical Text Mining and Ontologies
- DNA Repair Mechanisms
- Cancer Genomics and Diagnostics
- Prostate Cancer Treatment and Research
- Genomics and Chromatin Dynamics
- Radiopharmaceutical Chemistry and Applications
- Ubiquitin and proteasome pathways
- Computational Drug Discovery Methods
- Protein Degradation and Inhibitors
- Ferroptosis and cancer prognosis
- Metastasis and carcinoma case studies
- Cancer-related Molecular Pathways
- Gene expression and cancer classification
- Glioma Diagnosis and Treatment
- Cancer therapeutics and mechanisms
- Microtubule and mitosis dynamics
- Hippo pathway signaling and YAP/TAZ
- Cancer Immunotherapy and Biomarkers
- interferon and immune responses
- Epigenetics and DNA Methylation
Bayer (Germany)
2017-2024
The Netherlands Cancer Institute
2012-2023
Cancer Genomics Centre
2012-2016
Oncode Institute
2014-2015
Erasmus MC Cancer Institute
2013
Sanford Health
2013
Dana-Farber Cancer Institute
2013
Max Planck Institute for Informatics
2006-2012
AstraZeneca (Netherlands)
2012
Max Planck Society
2006-2009
Gene Ontology (GO) is a standard vocabulary of functional terms and allows for coherent annotation gene products. These annotations provide basis new methods that compare products regarding their molecular function biological role. We present method comparing sets GO assessing the similarity The relies on two semantic measures; sim Rel funSim. One measure (sim ) applied in comparison processes found different groups organisms. other (funSim) used to find functionally related within same or...
SummaryInhibitors of the ALK and EGF receptor tyrosine kinases provoke dramatic but short-lived responses in lung cancers harboring EML4-ALK translocations or activating mutations EGFR, respectively. We used a large-scale RNAi screen to identify MED12, component transcriptional MEDIATOR complex that is mutated cancers, as determinant response EGFR inhibitors. MED12 part cytoplasmic where it negatively regulates TGF-βR2 through physical interaction. suppression therefore results activation...
In most colorectal cancer (CRC) patients, outcome cannot be predicted because tumors with similar clinicopathological features can have differences in disease progression and treatment response. Therefore, a better understanding of the CRC biology is required to identify those patients who will benefit from chemotherapy find more tailored therapy plan for other patients. Based on unsupervised classification whole genome data 188 stages I–IV molecular was developed that consist at least three...
There are no effective therapies for the ~30% of human malignancies with mutant RAS oncogenes. Using a kinome-centered synthetic lethality screen, we find that suppression ERBB3 receptor tyrosine kinase sensitizes KRAS lung and colon cancer cells to MEK inhibitors. We show inhibition results in MYC-dependent transcriptional upregulation ERBB3, which is responsible intrinsic drug resistance. Drugs targeting both EGFR ERBB2, each capable forming heterodimers can reverse unresponsiveness by...
Abstract Background Colorectal cancer (CRC) is a heterogeneous and biologically poorly understood disease. To tailor CRC treatment, it essential to first model this heterogeneity by defining subtypes of patients with homogeneous biological clinical characteristics second match these cell lines for which extensive pharmacological data available, thus linking targeted therapies most likely respond treatment. Methods We applied new unsupervised, iterative approach stratify tumor samples into...
The DNA damage response (DDR) secures the integrity of genome eukaryotic cells. DDR deficiencies can promote tumorigenesis but concurrently may increase dependence on alternative repair pathways. ataxia telangiectasia and Rad3-related (ATR) kinase plays a central role in by activating essential signaling pathways repair. Here, we studied effect novel selective ATR inhibitor BAY 1895344 tumor cell growth viability. Potent antiproliferative activity was demonstrated broad spectrum human lines....
Alternative premessenger RNA splicing enables genes to generate more than one gene product. Splicing events that occur within protein coding regions have the potential alter biological function of expressed and even create new functions. has been suggested as explanation for discrepancy between number human functional complexity. Here, we carry out a detailed study alternatively spliced products annotated in ENCODE pilot project. We find alternative is frequent commonly suggested,...
Abstract Invasive lobular carcinoma (ILC) is the second most frequently occurring histological breast cancer subtype after invasive ductal (IDC), accounting for around 10% of all cancers. The molecular processes that drive development ILC are still largely unknown. We have performed a comprehensive genomic, transcriptomic and proteomic analysis large patient cohort present here an integrated portrait ILC. Mutations in CDH1 PI3K pathway frequent alterations identified two main subtypes ILCs:...
Recent observations connected DNA cytosine deaminase APOBEC3B to the genetic evolution of breast cancer. We addressed whether is associated with cancer clinical outcomes. messenger RNA (mRNA) levels were related in 1,491 primary cancers disease-free (DFS), metastasis-free (MFS), and overall survival (OS). For independent validation, mRNA expression was patient outcome data five additional cohorts (over 3,500 cases). In univariate Cox regression analysis, increasing as a continuous variable...
Abstract Motivation: Many hereditary human diseases are polygenic, resulting from sequence alterations in multiple genes. Genomic linkage and association studies commonly performed for identifying disease-related Such often yield lists of up to several hundred candidate genes, which have be prioritized validated further. Recent discovered that genes involved phenotypically similar functionally related on the molecular level. Results: Here, we introduce MedSim, a novel approach ranking...
Significance Poly(ADP-ribose) polymerase (PARP) inhibitors hold promise for patients with breast cancer 1 ( BRCA1 )-associatated cancers but are anticipated to give rise resistance. We show that mouse mammary tumors resembling BRCA1-associated metaplastic carcinoma display intrinsic resistance the PARP inhibitor olaparib as a result of increased P-glycoprotein drug efflux transporter expression. These findings may have implications ongoing clinical trials.
Abstract The lactate transporter SLC16A1/monocarboxylate 1 (MCT1) plays a central role in tumor cell energy homeostasis. In cell-based screen, we identified novel class of MCT1 inhibitors, including BAY-8002, which potently suppress bidirectional transport. We investigated the antiproliferative activity BAY-8002 panel 246 cancer lines and show that hematopoietic cells, particular diffuse large B-cell lymphoma lines, subsets solid models are particularly sensitive to inhibition. Associated...
Functional similarity based on Gene Ontology (GO) annotation is used in diverse applications like gene clustering, expression data analysis, protein interaction prediction and evaluation. However, there exists no comprehensive resource of functional values although such a database would facilitate the use measures different applications. Here, we describe FunSimMat (Functional Similarity Matrix, http://funsimmat.bioinf.mpi-inf.mpg.de/), large new that provides several semantic for GO terms....
The inhibitor telaprevir (VX-950) of the hepatitis C virus (HCV) protease NS3-4A has been tested in a recent phase 1b clinical trial patients infected with HCV genotype 1. This revealed residue mutations that confer varying degrees drug resistance. In particular, two positions V36A/G/L/M and T54A/S were associated low to medium levels resistance during viral breakthrough, together only an intermediate reduction replication fitness. These are located protein interior far away from ligand...
Abstract Pan- or multidrug resistance is a central problem in clinical oncology. Here, we use genetically engineered mouse model of BRCA2-associated hereditary breast cancer to study drug several types chemotherapy and PARP inhibition. We found that was strongly associated with an EMT-like sarcomatoid phenotype high expression the Abcb1b gene, which encodes efflux transporter P-glycoprotein. Inhibition P-glycoprotein could partly resensitize tumors inhibitor olaparib, docetaxel, doxorubicin....
Background Targeted thorium-227 conjugates (TTCs) are an emerging class of targeted alpha therapies (TATs). Their unique mode action (MoA) is the induction difficult-to-repair clustered DNA double-strand breaks. However, thus far, their effects on immune system largely unknown. Here, we investigated immunostimulatory mesothelin-targeted conjugate (MSLN-TTC) in vitro and vivo monotherapy combination with inhibitor checkpoint programmed death receptor ligand 1 (PD-L1) immunocompetent mice....
Abstract Large amounts of human protein interaction data have been produced by experiments and prediction methods. However, the experimental coverage interactome is still low in contrast to predicted data. To gain insight into value publicly available network data, we compared datasets, high‐throughput results from yeast two‐hybrid screens, literature‐curated protein‐protein interactions. This evaluation not only important for further methodological improvements, but also increasing...
Fra-1 (Fos-related antigen-1) is a member of the AP-1 (activator protein-1) family transcription factors. We previously showed that necessary for breast cancer cells to metastasize in vivo, and classifier comprising genes are expressed Fra-1-dependent fashion can predict outcome. Here, we show plays an important role also colon progression. Whereas depletion does not affect 2D proliferation human cells, it impairs growth soft agar suspension. Consistently, subcutaneous tumors formed by...
3511 Background: Recently, a number of independent groups reported novel molecular subtypes in colorectal cancer (CRC). A formal comparison across these classifiers is needed to reconcile findings and accelerate clinical translation. The CRCSC was formed identify consensus among the subtyping systems through large scale data sharing meta-analysis. Methods: consists 6 (15+ institutions) that analyzed more than 30 patient cohorts with gene expression data, spanning multiple platforms sample...