A5048279582- Sarcoma Diagnosis and Treatment
- Gastrointestinal Tumor Research and Treatment
- Peptidase Inhibition and Analysis
- Systemic Lupus Erythematosus Research
- Rheumatoid Arthritis Research and Therapies
- Cardiac tumors and thrombi
- Metastasis and carcinoma case studies
- Soft tissue tumors and treatment
- Monoclonal and Polyclonal Antibodies Research
- Cancer Genomics and Diagnostics
- Cell Adhesion Molecules Research
- Gastric Cancer Management and Outcomes
German Cancer Research Center
2024-2025
Deutschen Konsortium für Translationale Krebsforschung
2022-2025
Essen University Hospital
2022-2023
University of Duisburg-Essen
2022
University of Nebraska Medical Center
2020
Brigham and Women's Hospital
2014
Harvard University
2014
Imatinib resistance in GI stromal tumors (GISTs) is primarily caused by secondary
Gastrointestinal stromal tumors (GIST), driven by KIT and PDGFRA mutations, are the most common mesenchymal of gastrointestinal tract. Although tyrosine kinase inhibitors (TKIs) have advanced treatment, resistance mutations off-target toxicity limit their efficacy. This study develops covalent TKIs targeting drug-resistant GIST through structure-based design, synthesis, biological evaluation. SAR studies provided key insights into mutant interactions, first crystal structure bound to a...
Circulating tumor DNA (ctDNA) from circulating free (cfDNA) in GIST is of interest for the detection heterogeneous resistance mutations and treatment monitoring. However, methodologies use a local setting are not standardized error-prone difficult to interpret. We established workflow evaluate routine tissue NGS (Illumina-based next generation sequencing) panels pipelines ctDNA sequencing an academic setting. Regular blood collection (Sarstedt) EDTA tubes were sufficient direct processing...
Abstract Introduction: Ripretinib (Rip) is a kinase inhibitor with broad preclinical activity against mutant KIT. Based on the INVICTUS trial, Rip was approved for patients Gastrointestinal Stromal Tumors (GIST) after treatment 3 or more inhibitors. Most in this ≥4th-line setting progress within one year. Here, we characterized Rip-progressing GIST samples to identify resistance mechanisms. Methods: Progressing lesions 25 were analyzed by NGS failure. KIT mutations (muts) recapitulated gene...