Markus Eckstein

Dec 30, 2024 | nature.com | Charlie Saillard |Philipp Mann |Charles Maussion |Niklas Klümper |Johannes Breyer |Ralph E. Wirtz | +9 more

Pathogenic activating mutations in the fibroblast growth factor receptor 3 (FGFR3) drive disease maintenance and progression in urothelial cancer. 10–15% of muscle-invasive and metastatic urothelial cancer (MIBC/mUC) are FGFR3-mutant. Selective targeting of FGFR3 hotspot mutations with tyrosine kinase inhibitors (e.g., erdafitinib) is approved for mUC and requires FGFR3 mutational testing. However, current testing assays (polymerase chain reaction or next-generation sequencing) necessitate high tissue quality, have long turnover time, and are expensive. To overcome these limitations, we develop a deep-learning model that detects FGFR3 mutations using routine hematoxylin-eosin slides. Encompassing 1222 cases, our study is a large-scale validation of a model prescreening FGFR3 mutations for MIBC and mUC patients. In this work, we demonstrate that our model achieves high sensitivity (>93%) on advanced and metastatic cases while reducing molecular testing by 40% on average, thereby offering a cost-effective and rapid pre-screening tool for identifying patients eligible for FGFR3 targeted therapies. Detecting FGFR3-mutant muscle-invasive and metastatic urothelial cancers (MIBC/mUC) for targeted therapy remains challenging, but clinically important. Here, the authors develop a deep-learning model to detect FGFR3 mutations in MIBC/mUC from routine histopathology slides, allowing for highly sensitive, rapid, and cost-effective pre-screening.

Sep 23, 2024 | europeanurology.com | Markus Eckstein

Get full text accessLog in, subscribe or purchase for full access. ReferencesKlumper N, Grunwald V, Hartmann A, Holzel M, Eckstein M. The role of microsatellite instability/DNA mismatch repair deficiency and tumor mutational burden as biomarkers in predicting response to immunotherapy in castration-resistant prostate cancer. Eur Urol, in press. https://doi.org/10.1016/j.eururo.2024.04.026. Abida, W. ∙ Cheng, M.L. ∙ Armenia, J. ...

Sep 2, 2024 | europeanurology.com | Sandy Figiel |Anthony Bates |David Braun |Renu S. Eapen |Markus Eckstein |Brandon Manley | +5 more

KeywordsGenomicsTranscriptomicsProteomicsUrological cancer1 IntroductionAlbert Einstein famously said: “Look deep into nature, and then you will understand everything better”, and although he wrote this 2 yr before Francis Crick and James Watson [1]1. Watson, J.D. ∙ Crick, F.H.C.Molecular structure of nucleic acids: a structure for deoxyribose nucleic acidNature. 1953; 171:737-738 discovered DNA, he may well have had genes in mind.

Jul 30, 2024 | nature.com | Leticija Zlatar |Markus Eckstein |Rostyslav Bilyy |Georg Schett |Rebecca C. Chukwuanukwu

AbstractTuberculosis (TB) remains one of the top 10 causes of death worldwide and still poses a serious challenge to public health. Recent attention to neutrophils has uncovered unexplored areas demanding further investigation. Therefore, the aim of this study was to determine neutrophil activation and circulatory neutrophil extracellular trap (NET) formation in various types of TB.

Apr 26, 2024 | nature.com | Milena L Pachowsky |Markus Eckstein |Stefano Alivernini |Maria-Antonietta D’Agostino |Georg Schett

AbstractBispecific T cell engagers (BiTEs) kill B cells by engaging T cells. BiTEs are highly effective in acute lymphoblastic leukemia. Here we treated six patients with multidrug-resistant rheumatoid arthritis (RA) with the CD19xCD3 BiTE blinatumomab under compassionate use. Low doses of blinatumomab led to B cell depletion and concomitant decrease of T cells, documenting their engager function.