Pharmacophenotypic analysis of advanced pancreatic cancer patient-derived tumoroid models uncovers spatiotemporal drug resistance dynamics associated with single-agent and combination therapies (AACRPanCa 2026) - Oct 15, 2026 - Abstract #B042; "Drug screening revealed extensive inter-patient variability in sensitivity and resistance to standard-of-care, off-label, and investigational therapies, including the KRAS G12D inhibitor MRTX1133, the RAS(ON) inhibitors daraxonrasib (panRAS) and zoldonrasib (KRAS G12D), and the PRMT5 inhibitors MRTX1719 and vopimetostat...A focused set of clinically relevant combinations, including paclitaxel, gemcitabine, 5-fluorouracil, daraxonrasib, and zoldonrasib, demonstrated additive or synergistic activity across subsets of PDT models...Spatiotemporal pharmacophenotypic profiling reveals profound intra-patient and inter-patient heterogeneity in drug response and resistance evolution in pancreatic cancer. These findings support the use of longitudinal phenotypic analysis to identify resistance-associated cellular states and to guide the development of rational combination therapies capable of improving the durability of response to RAS-targeted treatment..."
Clinical • Combination therapy • Metastases • Oncology • Pancreatic Cancer • Solid Tumor • KRAS
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Jarle Bruun; Peter W. Eide; Christer A. Andreassen; Nicolas Pasquier; Tine N. Alver; Christina Biörserud; Sara Blomström; Åke A. Sandberg; Elena Rangelova
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