A5008015466- Lung Cancer Treatments and Mutations
- Lung Cancer Research Studies
- Peptidase Inhibition and Analysis
- Cancer Immunotherapy and Biomarkers
- Cancer Genomics and Diagnostics
- Cancer, Hypoxia, and Metabolism
- HER2/EGFR in Cancer Research
- Cancer Research and Treatments
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Colorectal Cancer Treatments and Studies
- Cancer therapeutics and mechanisms
- Cancer Cells and Metastasis
- Immune cells in cancer
- Neuroendocrine Tumor Research Advances
- Glycosylation and Glycoproteins Research
- Angiogenesis and VEGF in Cancer
- Monoclonal and Polyclonal Antibodies Research
- Cancer-related Molecular Pathways
- Gastric Cancer Management and Outcomes
- Radiomics and Machine Learning in Medical Imaging
- Glioma Diagnosis and Treatment
- Immunotherapy and Immune Responses
- Ferroptosis and cancer prognosis
- Lung Cancer Diagnosis and Treatment
- Cancer, Lipids, and Metabolism
University Hospital Cologne
2015-2024
University of Cologne
2015-2024
Evotec (Germany)
2010-2024
Centrum für Integrierte Onkologie
2016-2021
Universitätsmedizin Göttingen
2013
Evotec (United States)
2012
Klinikum Bremen-Mitte
2012
University of Göttingen
2009-2010
To identify novel mechanisms of resistance to third-generation EGFR inhibitors in patients with lung adenocarcinoma that progressed under therapy either AZD9291 or rociletinib (CO-1686).
Small cell lung cancer and extrapulmonary small carcinomas are the most aggressive type of neuroendocrine carcinomas. Clinical treatment relies on conventional chemotherapy radiotherapy; relapses frequent. The PD-1/PD-L1/PD-L2 pathway is a major target anti-tumour immunotherapy. Aberrant PD-L1 or PD-L2 expression may cause local immune-suppression. Here we investigated PD-1 its ligands by immunohistochemistry RNA-seq in carcinomas.PD-L1 protein were analysed 94 clinical cases (61 pulmonary,...
IntroductionAlthough KRAS mutations in NSCLC have been considered mutually exclusive driver for a long time, there is now growing evidence that KRAS-mutated represents genetically heterogeneous subgroup. We sought to determine genetic heterogeneity with respect cancer-related co-mutations and their correlation different mutation subtypes.MethodsDiagnostic samples from 4507 patients were analyzed by next-generation sequencing using panel of 14 genes and, subset patients, fluorescence situ...
Abstract The evolutionary processes that underlie the marked sensitivity of small cell lung cancer (SCLC) to chemotherapy and rapid relapse are unknown 1–3 . Here we determined tumour phylogenies at diagnosis throughout immunotherapy by multiregion sequencing 160 tumours from 65 patients. Treatment-naive SCLC exhibited clonal homogeneity distinct sites, whereas first-line platinum-based led a burst in genomic intratumour heterogeneity spatial diversity. We observed branched evolution shift...
Abstract The emergence of acquired resistance against targeted drugs remains a major clinical challenge in lung adenocarcinoma patients. In subgroup these patients we identified an association between selection EGFR T790M -negative but G724S -positive subclones and osimertinib resistance. We demonstrate that limits the activity third-generation inhibitors both vitro vivo. Structural analyses computational modeling indicate mutations may induce conformation glycine-rich loop, which is...
Inhibition of the PD-1/PD-L1 pathway may induce anticancer immune responses in non-small cell lung cancer (NSCLC). Two PD-L1 immunohistochemistry (IHC) assays have been approved as companion diagnostic tests for therapeutic anti-PD-1 antibodies. However, many aspects prevalence and association with genetically defined subtypes not addressed systematically. Here, we analyzed expression 436 annotated NSCLC specimens enriched early stages using antibody 5H1. Expression was detected tumor cells...
Purpose: Programmed death ligand-1 (PD-L1), encoded by the CD274 gene, is a target for immune checkpoint blockade; however, little known about genomic alterations. A subset of small-cell lung cancer (SCLC) exhibits increased copy number chromosome 9p24, on which resides; most SCLCs show low expression PD-L1. We therefore examined whether recurrent alterations.Experimental Design: somatic alterations in two patient cohorts quantitative real-time PCR 72 human SCLC cases (cohort 1) and SNP...
Abstract Glioblastoma (GBM) is a non-T-cell–inflamed cancer characterized by an immunosuppressive microenvironment that impedes dendritic cell maturation and T-cell cytotoxicity. Proangiogenic cytokines such as VEGF angiopoietin-2 (Ang-2) have high expression in glioblastoma cell-specific manner not only drive tumor angiogenesis vascular permeability but also negatively regulate T-lymphocyte innate immune responses. Consequently, the alleviation of immunosuppression might be prerequisite for...
IntroductionTP53 and KEAP1 are frequently mutated in NSCLC, but their prognostic value is ambiguous, particularly localized stage tumors.MethodsThis retrospective cohort study included a total of 6297 patients with NSCLC who were diagnosed between November 1998 February 2020. The primary end point was overall survival. Patients central pathology laboratory as part the Network Genomic Medicine collaboration, encompassing more than 300 lung cancer-treating oncology centers Germany. All...
Overexpression of the human epidermal growth factor receptor-2 (HER2) in breast cancer strongly correlates with aggressive tumors and poor prognosis. Recently, a positive correlation between HER2 MIF (macrophage migration inhibitory factor, tumor-promoting protein heat-shock 90 (HSP90) client) levels was shown cells. However, underlying mechanistic link remained unknown. Here we show that overexpressed constitutively activates 1 (HSF1), master transcriptional regulator inducible proteotoxic...
Purpose: We sought to investigate the clinical response MET inhibition in patients diagnosed with structural alterations and characterize their functional relevance cellular models.Experimental Design: Patients were selected for treatment crizotinib upon results of hybrid capture-based next-generation sequencing. To confirm observations, we analyzed models that express these kinase alterations.Results: Three individual identified harbor within receptor. Two showed genomic rearrangements,...
Aims Programmed death ligand 1 ( PD ‐L1) immunohistochemistry has become a mandatory diagnostic test in the treatment of lung cancer. Several research initiatives have started to harmonise five ‐L1 assays that been used clinical trials. Here, we report data on interlaboratory and interassay concordance for commercial (‘assays’) laboratory‐developed tests LDT s) at 10 German testing sites. Methods results To assess concordance, tissue microarray containing 21 pulmonary carcinoma specimens was...
Abstract Background PD-1/PD-L1-Immunotherapy has been approved for gastric carcinoma. PD-L1 assessment by immunohistochemistry is the principle biomarker. Are biopsies able to map actual status of entire tumor? Methods Whole tumor slides 56 carcinoma were analyzed determine distribution positive cells in areas. Tissue micro arrays with four cores surface, which represents endoscopically accessible biopsy zone, built from same tumors. The CPS value was determined separately each core....
Context.— Recently, a new type of antibody-drug conjugate, trastuzumab-deruxtecan (T-DXd), has been approved for the treatment metastatic breast cancer with low level human epidermal growth factor receptor 2 (HER2) gene expression. Thereby, eligibility relies on an accurate diagnosis HER2-low status defined by immunohistochemistry IHC 1+/2+ no amplification. Objective.— To assess pathologists’ accuracy and training efficacy in HER2-low. Design.— Agreement rates scoring tissue were assessed...
Huntington's disease (HD) is associated with increased expression levels and activity of tissue transglutaminase (TG2), an enzyme primarily known for its cross-linking proteins. To validate TG2 as a therapeutic target HD in transgenic models eventual clinical development, selective brain-permeable inhibitor required. Here, comprehensive profiling platform biochemical cellular assays presented which has been established to evaluate the potency, efficacy, subtype selectivity...
Tissue transglutaminase 2 (TG2) is a multifunctional protein primarily known for its calcium-dependent enzymatic cross-linking activity via isopeptide bond formation between glutamine and lysine residues. TG2 overexpression have been found to be associated with Huntington's disease (HD); specifically, up-regulated in the brains of HD patients animal models disease. Interestingly, genetic deletion two different mouse models, R6/1 R6/2, results improved phenotypes including reduction neuronal...
The epidermal growth factor receptor (EGFR) is a widely expressed Ag that successfully targeted in tumor patients by mAbs or tyrosine kinase inhibitors. A clinical study non-small cell lung cancer demonstrated positive correlation between EGFR expression levels and the therapeutic efficacy of mAb cetuximab. However, impact on different mechanisms action (MoAs) triggered has not been defined. In this study, BHK-21 cells were stably transfected to express levels, which quantified...
An examination of the activity profiles RET inhibitors suggests potential treatment for -rearranged cancers.
The anaplastic lymphoma kinase (ALK) rearrangement defines a distinct molecular subtype of non-small cell lung cancer (NSCLC). Despite the excellent initial efficacy ALK inhibitors in patients with ALK+ cancer, resistance occurs almost inevitably. To date, there is no reliable biomarker allowing identification at higher risk relapse. Here, we analysed subset 53 tumours and without TP53 mutation NSCLC lines by NanoString nCounter technology. We found that co-occurrence early mutations can...