The epidermal growth factor receptor (EGFR) kinase inhibitor osimertinib is a first-line treatment of non-small cell lung cancer with oncogenic driver mutations in EGFR, while anaplastic lymphoma kinase (ALK)-positive NSCLC is treated with ALK inhibitors (crizotinib, alectinib, lorlatinib). These targeted therapies have significantly improved progression-free survival in NSCLC and are well tolerated. However, resistance inevitably arises. At the EORTC-NCI-AACR (ENA) symposium on Molecular Targets and Cancer Therapeutics, Janneke Melis of Oncolines will present the molecular profiling of NSCLC cell lines that were selected in vitro for resistance against the EGFR inhibitor osimertinib, the ALK inhibitor crizotinib or the KRAS(G12C) inhibitor sotorasib. The cell lines were generated at Pangaea Oncology, a collaborating partner of Oncolines, by culturing the cells in medium containing an increasing concentration of inhibitor. At Oncolines, the cell lines were examined for cross-resistance against drugs targeting the same primary target. In addition, the cell lines were profiled with a library of small molecule compounds targeting commonly occurring resistance mechanisms, with the aim to determine which drugs may effectively overcome the resistance and which molecular mechanisms could play a role. The poster will be presented on Friday, the last day of the conference, and will be displayed at poster board PB371. Title of the poster: “Characterization of cancer cell lines selected for resistance to tyrosine kinase inhibitors and signal transduction therapies“.