EP08.02-079 The Use of Lung Adenocarcinoma Patient-Derived Xenografts and Organoids to Study GDP-KRAS G12C Inhibitor Resistance

KRAS-mutations are present in 25-30% of the most common form of lung cancer, lung adenocarcinoma (LUAD), and KRASG12C mutations account for 40% of KRAS-mutations in LUAD. Recent development of covalent GDP-KRASG12C inhibitors (G12Ci) have reignited efforts to target the once “undruggable” protein. Preclinical studies have identified mechanisms of adaptive resistance in cell lines. However, patient-derived xenografts (PDX) and xenograft-derived organoids (XDO) have not yet been extensively used to study mechanisms of primary and acquired resistance.