New Molecular Target Identified in High-Risk Neuroblastoma
Researcher at the University Hospital Cologne and the Faculty of Medicine at the University of Cologne have identified a genetic alteration in the FGFR1 gene in a small group of children with neuroblastoma that is associated with a particularly aggressive disease course. Preclinical studies suggest that targeted drugs - so-called FGFR inhibitors - can significantly suppress tumor growth in relevant models, offering a potential approach for future personalized therapies. The findings were published in the study “Mutated FGFR1 is an oncogenic driver and therapeutic target in high-risk neuroblastoma” in the Journal of Clinical Investigation.
Neuroblastoma is one of the most common cancers in childhood. About half of affected children require intensive multimodal treatment, including surgery, chemotherapy, radiation therapy, and additional therapeutic approaches. Despite these intensive treatments, currently only about half of children with high-risk neuroblastoma can be cured. Prognosis is particularly poor for tumors that respond inadequately to therapy or recur after an initial successful treatment.
In the study, researchers first investigated the biological effects of this mutation in cell cultures and subsequently in mouse models. They found that the FGFR1 alteration can significantly accelerate tumor cell growth. At the same time, targeted drugs from the class of FGFR inhibitors were shown to strongly suppress the growth of these tumor cells. This effect was also observed in tumor models that had previously failed to respond to conventional chemotherapy.
Based on these preclinical findings, a patient with FGFR1-mutated neuroblastoma was treated with a corresponding agent for the first time. The FGFR inhibitor futibatinib was administered in combination with low-dose chemotherapy to a child with chemotherapy-resistant neuroblastoma. This resulted in the first observed partial tumor regression.
“Our work clearly demonstrates that this FGFR1 mutation is associated with an aggressive course of neuroblastoma and is often linked to failure of current standard therapies,” said the study’s first author, Dr. Lisa Werr from the Department of Pediatrics and Adolescent Medicine at University Hospital Cologne. “Our investigations were crucial in demonstrating the potential effectiveness of FGFR inhibitors in neuroblastomas with this mutation and in paving the way for their clinical application. The goal of further studies is to significantly improve the chances of cure for affected children through targeted therapy.”
FGFR-targeted therapies already play a role in personalized treatment approaches in adult oncology. “However, the potential benefit of such drugs in neuroblastoma patients has not been studied to date,” said Prof. Dr. Matthias Fischer, head of Experimental Pediatric Oncology at University Hospital Cologne and Principal Investigator at the Center for Molecular Medicine Cologne (CMMC).“Our findings suggest that targeted therapies with FGFR inhibitors could become a new treatment option for children with this genetic alteration in the future.”
Original Publication
https://www.jci.org/articles/view/189152
Lisa Werr*, Jana Boland,Josephine Petersen, Fiorella Iglesias, Stefanie Höppner, Christoph Bartenhagen, Carolina Rosswog, Anna-Maria Hellmann, Yvonne Kahlert, Nadine Hemstedt, Nadliv Ibruli, Marcel A. Dammert, Boris Decarolis, Jan-Michael Werner, Florian Malchers, Kathrin Schramm, Olaf Witt, Klaus H. Beiske, Anne Gro Wesenberg Rognlien, Maria Winther Gunnes, Karin P. Langenberg, Jan Molenaar, Marie Bernkopf, Sabine Taschner-Mandl, Debbie Hughes, Sally L. George, Louis Chesler, Johannes H. Schulte, Giuseppe Barone, Mario Capasso, Lea F. Surrey, Rochelle Bagatell, Julien Masliah-Planchon, Gudrun Schleiermacher, Holger Grüll, Frank Westermann, Anne M. Schultheis, Reinhard Büttner, Anton G. Henssen, Angelika Eggert, Martin Peifer, Neerav N. Shukla, Thorsten Simon, Barbara Hero, H. Christian Reinhardt, Roman K. Thomas, and Matthias Fischer*, "Mutated FGFR1 is an oncogenic driver and therapeutic target in high-risk neuroblastoma", Journal of Clinical Investigation, 2025. DOI: 10.1172/JCI189152
Authors with CMMC affiliation indicated in bold and leading / first authors are indicated with a star (*) .
This message has been modified by the CMMC (K. Heber & D. Grosskopf-Kroiher) and is based on the text by the press and communications teams of the University Hospoital Cologne (original German version here).