Quantifying Treatment Resistance in Mixtures of Gastrointestinal Stromal Tumor Cells with BARMIX
Darbalaei, M.; Muhlenberg, T.; Zummack, J.; Dujardin, P.; Grunewald, S.; Baginska, A.; Munteanu, P.; Martinez Cruz, M.; Dorsch, M.; Schramm, A.; Bauer, S.; Hoffmann, D.; Gruner, B. M.
Show abstract
Targeted therapies in gastrointestinal stromal tumors (GIST) often fail due to heterogeneous resistance mutations arising across metastatic sites. Efficient, rational design of mutation-specific therapies requires the ability to quantify treatment resistance across many genotypes in parallel. Here, we present BARcode MIXture analysis (BARMIX), a platform combining multiplexed experiments with DNA-barcoded cancer cell mixtures in vitro and in vivo, and a probabilistic framework for quantitative assessment of genotype-specific treatment resistance. BARMIX efficiently and accurately recapitulated known clinical resistance patterns in GIST and matched resistance measurements from individual cell lines in vitro and in vivo. This experimental-computational approach provides a scalable and broadly applicable strategy for quantifying treatment responses in complex cell populations, enabling systematic preclinical testing of new drugs and combinations to identify mutation-specific therapeutic options for precision oncology in GIST and beyond.
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