Heathcliff Dorado García, Fabian Pusch, Yi Bei, Jennifer von Stebut, Glorymar Ibáñez, Kristina Guillan, Koshi Imami, Dennis Gürgen, Jana Rolff, Konstantin Helmsauer, Stephanie Meyer-Liesener, Natalie Timme, Victor Bardinet, Rocío Chamorro González, Ian C MacArthur, Celine Y Chen, Joachim Schulz, Antje M Wengner, Christian Furth, Birgit Lala, Angelika Eggert, Georg Seifert, Patrick Hundsoerfer, Marieluise Kirchner, Philipp Mertins, Matthias Selbach, Andrej Lissat, Frank Dubois, David Horst, Johannes H Schulte, Simone Spuler, Daoqi You, Filemon Dela Cruz, Andrew L Kung, Kerstin Haase, Michela DiVirgilio, Monika Scheer, Michael V Ortiz, Anton G Henssen
Despite advances in multi-modal treatment approaches, clinical outcomes of patients suffering from PAX3-FOXO1 fusion oncogene-expressing alveolar rhabdomyosarcoma (ARMS) remain dismal. Here we show that PAX3-FOXO1-expressing ARMS cells are sensitive to pharmacological ataxia telangiectasia and Rad3 related protein (ATR) inhibition. Expression of PAX3-FOXO1 in muscle progenitor cells is not only sufficient to increase sensitivity to ATR inhibition, but PAX3-FOXO1-expressing rhabdomyosarcoma cells also exhibit increased sensitivity to structurally diverse inhibitors of ATR...
July 25, 2022: Nature Communications