Antineoplastic efficacy profiles of avapritinib and nintedanib in KIT D816V+ systemic mastocytosis: a preclinical study.
Year: 2023
Type: article
Abstract: : 0.1-5 µM). Growth-inhibitory effects of avapritinib and nintedanib were accompanied by signs of apoptosis and decreased surface expression of the transferrin receptor CD71 in neoplastic MC. Finally, we were able to show that avapritinib counteracts IgE-dependent histamine secretion in basophils and MC in patients with SM. These effects of avapritinib may explain the rapid clinical improvement seen during treatment with this KIT inhibitor in patients with SM. In conclusion, avapritinib and nintedanib are new potent inhibitors of growth and survival of neoplastic MC expressing various KIT mutant forms, including D816V, V560G, and K509I, which favors the clinical development and application of these new drugs in advanced SM. Avapritinib is of particular interest as it also blocks mediator secretion in neoplastic MC.
Source: PubMed Central
Authors: Lina Degenfeld-Schonburg, Susanne Gamperl, Gabriele Stefanzl, Anna-Katharina Schruef, Irina Sadovnik, Karin Bauer, Dubravka Smiljkovic, Gregor Eisenwort, Barbara Peter, Georg Greiner, Emir Hadzijusufovic, Juliana Schwaab, Wolfgang R Sperr, Gregor Hoermann, Sonja Kopanja, Zsolt Szépfalusi, Konrad Hoetzenecker, Peter Jaksch, Andreas Reiter, Michel Arock, Peter Valent
Institutions: Medical University of Vienna, Ludwig Boltzmann Institute for Hematology and Oncology, University of Veterinary Medicine Vienna, Heidelberg University, University Medical Centre Mannheim, Medizinische Fakultät Mannheim, Munich Leukemia Laboratory (Germany), Pitié-Salpêtrière Hospital, Université Pierre-et-Marie-Curie
Language: English
Topic: Mast cells and histamine
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funders: Austrian Science Fund, Universität Wien
OpenAlex ID: W4323810481