Resistance Profiling Using Functional Imaging and Next Generation Sequencing in Refractory Gastrointestinal Stomal Tumors (GIST)

Gastrointestinal stromal tumors (GIST) are the most common malignant sarcomas of the gastrointestinal tract. Inhibitors of the mutated driver proteins KIT and PDGFRA can temporarily control disseminated GIST disease but cannot cure it. Recently, the investigators were able to elucidate the two main resistance mechanisms-the coexistence of ATP-binding pocket (AP) and activation loop (AL) mutations, as well as AP/AL combination mutations. Determining these resistance factors requires methods that are not yet established in routine clinical practice. The investigators hypothesize that identifying these factors and creating resistance profiles in the context of the anatomical location of metastatic lesions can open up new, clinically relevant therapeutic options, including local therapies. The aim of this project is to evaluate the practicability of these methods in everyday clinical use. An AI-supported image analysis and specialized molecular methods will be combined into a comprehensive resistance profile and will be provided to the treating physicians to potentially guide treatment decisions.