Thomas Mühlenberg, Johanna Falkenhorst, Tom Schulz, Benjamin S Fletcher, Alina Teuber, Dawid Krzeciesa, Isabella Klooster, Meijun Lundberg, Lydia Wilson, Jonas Lategahn, Margaret von Mehren, Susanne Grunewald, Alicia Isabell Tüns, Eva Wardelmann, Jason K Sicklick, Mehdi Brahmi, César Serrano, Hans-Ulrich Schildhaus, Sonja Sievers, Jürgen Treckmann, Michael C Heinrich, Chandrajit P Raut, Wen-Bin Ou, Adrian Marino-Enriquez, Suzanne George, Daniel Rauh, Jonathan A Fletcher, Sebastian Bauer
PURPOSE: Imatinib resistance in GI stromal tumors (GISTs) is primarily caused by secondary KIT mutations, and clonal heterogeneity of these secondary mutations represents a major treatment obstacle. KIT inhibitors used after imatinib have clinical activity, albeit with limited benefit. Ripretinib is a potent inhibitor of secondary KIT mutations in the activation loop (AL). However, clinical benefit in fourth line remains limited and the molecular mechanisms of ripretinib resistance are largely unknown...
February 26, 2024: Journal of Clinical Oncology