A5013721197- Lung Cancer Research Studies
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Metastasis and carcinoma case studies
- Cancer Immunotherapy and Biomarkers
- Histone Deacetylase Inhibitors Research
- Peptidase Inhibition and Analysis
- Radiopharmaceutical Chemistry and Applications
- Protein Degradation and Inhibitors
- Cytokine Signaling Pathways and Interactions
- Immune Cell Function and Interaction
- Lung Cancer Treatments and Mutations
- Immune cells in cancer
- Neuroendocrine Tumor Research Advances
- Synthesis and biological activity
- Cancer therapeutics and mechanisms
- Virus-based gene therapy research
- Protease and Inhibitor Mechanisms
- Cancer Research and Treatments
- Immunotherapy and Immune Responses
- Neuroblastoma Research and Treatments
- Advanced biosensing and bioanalysis techniques
- Medical Imaging Techniques and Applications
- Cancer, Hypoxia, and Metabolism
- Monoclonal and Polyclonal Antibodies Research
- RNA Interference and Gene Delivery
Rigshospitalet
2015-2025
Dana-Farber Cancer Institute
2014-2025
Copenhagen University Hospital
2007-2025
Harvard University
2013-2024
University of Bergen
2024
University of Copenhagen
2011-2023
Takeda (United States)
2023
Sygehus Sønderjylland
2023
IT University of Copenhagen
2022
Food Research Institute
2020
The success in lung cancer therapy with programmed death (PD)-1 blockade suggests that immune escape mechanisms contribute to tumor pathogenesis. We identified a correlation between EGF receptor (EGFR) pathway activation and signature of immunosuppression manifested by upregulation PD-1, PD-L1, CTL antigen-4 (CTLA-4), multiple tumor-promoting inflammatory cytokines. observed decreased CTLs increased markers T-cell exhaustion mouse models EGFR-driven cancer. PD-1 antibody improved the...
Small cell lung cancer (SCLC) patient-derived xenografts (PDX) can be generated from biopsies or circulating tumor cells (CTC), though scarcity of tissue and low efficiency growth have previously limited these approaches. Applying an established clinical-translational pipeline for collection automated microfluidic platform CTC enrichment, we 17 biopsy-derived PDXs CTC-derived in a 2-year timeframe, at 89% 38% efficiency, respectively. Whole-exome sequencing showed that somatic alterations...
Radiation therapy (RT), a critical modality in the treatment of lung cancer, induces direct tumor cell death and augments tumor-specific immunity. However, despite initial control, most patients suffer from locoregional relapse and/or metastatic disease following RT. The use immunotherapy non-small-cell cancer (NSCLC) could potentially change this outcome by enhancing effects Here, we report significant (up to 70% volume reduction target lesion) durable 12 weeks) regressions conditional...
Abstract Purpose: Small cell lung cancer (SCLC) is a highly malignant disease with poor prognosis, necessitating the need to develop new and efficient treatment modalities. PRIMA-1Met (p53-dependent reactivation of massive apoptosis), also known as APR-246, small molecule, which restores tumor suppressor function mutant p53 induces death in various types. Since mutated more than 90% SCLC, we investigated ability induce apoptosis inhibit growth SCLC different mutations. Experimental Design:...
Abstract Acquired drug resistance is a major factor limiting the effectiveness of targeted cancer therapies. Targeting tumors with kinase inhibitors induces complex adaptive programs that promote persistence fraction original cell population, facilitating eventual outgrowth inhibitor-resistant tumor clones. We show addition newly identified CDK7/12 inhibitor, THZ1, to therapy enhances killing and impedes emergence drug-resistant populations in diverse cellular vivo models. propose state...
A first-in-human clinical trial with Positron Emission Tomography (PET) imaging of the urokinase-type plasminogen activator receptor (uPAR) in patients breast, prostate and bladder cancer, is described. uPAR expressed many types human cancers expression predictive invasion, metastasis indicates poor prognosis. PET therefore holds promise to be a new innovative method for improved cancer diagnosis, staging individual risk stratification. The specific peptide AE105 was conjugated macrocyclic...
More than 90% of small cell lung cancers (SCLCs) harbor loss-of-function mutations in the tumor suppressor gene RB1 . The canonical function product, pRB, is to repress E2F transcription factor family, but pRB also functions regulate cellular differentiation part through its binding histone demethylase KDM5A (also known as RBP2 or JARID1A). We show that promotes SCLC proliferation and SCLC's neuroendocrine phenotype by sustaining expression ASCL1. Mechanistically, we found sustains ASCL1...
Abstract Small cell lung cancer (SCLC) presents as a highly chemosensitive malignancy but acquires cross-resistance after relapse. This transformation is nearly inevitable in patients has been difficult to capture laboratory models. Here, we present preclinical system that recapitulates acquired cross-resistance, developed from 51 patient-derived xenograft (PDX) Each model was tested vivo against three clinical regimens: cisplatin plus etoposide, olaparib temozolomide, and topotecan. These...
Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) have been discovered several cancer types cause the neurometabolic syndrome D2-hydroxyglutaric aciduria (D2HGA). The mutant enzymes exhibit neomorphic activity resulting production of acid (D-2HG). To study pathophysiological consequences accumulation D-2HG, we generated transgenic mice with conditionally activated IDH2 R140Q R172K alleles. Global induction expression adults resulted dilated cardiomyopathy, white matter abnormalities...
Predicting the outcome of immunotherapy is essential for efficient treatment.The recent clinical success increasingly changing paradigm cancer treatment.Accordingly, development immune-based agents accelerating and number in global immuno-oncology pipeline has grown 60-70% over past year.However, despite remarkable efficacy some patients, only few achieve a lasting response.Treatment failure can be attributed to poorly immunogenic tumors that do not attract tumor infiltrating lymphocytes...
Abstract Purpose Despite remarkable clinical responses and prolonged survival across several cancers, not all patients benefit from PD-1/PD-L1 immune checkpoint blockade. Accordingly, assessment of tumour PD-L1 expression by immunohistochemistry (IHC) is increasingly applied to guide patient selection, therapeutic monitoring, improve overall response rates. However, tissue-based methods are invasive prone sampling error. We therefore developed a PET radiotracer specifically detect in...
The overexpression of urokinase-type plasminogen activator receptors (uPARs) represents an established biomarker for aggressiveness in most common malignant diseases, including breast cancer (BC), prostate (PC), and urinary bladder (UBC), is therefore important target new therapeutic diagnostic strategies. In this study, uPAR PET imaging using a 68Ga-labeled version the uPAR-targeting peptide (AE105) was investigated group patients with BC, PC, UBC. aim first-in-human, phase I clinical trial...
Abstract Although EGFR mutant–selective tyrosine kinase inhibitors (TKI) are clinically effective, acquired resistance can occur by reactivating ERK. We show using in vitro models of TKI with a mesenchymal phenotype that CXCR7, an atypical G protein-coupled receptor, activates the MAPK–ERK pathway via β-arrestin. Depletion CXCR7 inhibited MAPK pathway, significantly attenuated resistance, and resulted mesenchymal-to-epithelial transition. overexpression was essential reactivation ERK1/2 for...
Antibody-based PET tracers are exceptionally well-suited for determination of the in vivo biodistribution and quantification therapeutic antibodies. The continued expansion antibody-based therapeutics has accordingly driven development towards more robust conjugation strategies order to reliably predict performance such agents. We therefore aimed evaluate effect site-specific labeling by enzymatic remodeling on stability, immuno-reactivity tumor-targeting properties monoclonal antibody (mAb)...