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Lung cancer is the most common cancer to metastasize to the brain, with 50% of all brain metastases originating from lung primary tumors. Traditional therapy for lung cancer brain metastases includes surgical resection, radiation, and chemotherapy. Due to the presence of the blood-tumor barrier, penetration of therapeutics is significantly hindered. Even when used in combination, tumor recurrence and regrowth after initial chemoradiotherapy remain a significant issue. To recapitulate recurrent disease, we aim to characterize a radio-resistant preclinical model of brain metastasis to investigate its effect on growth, chemosensitivity, and drug permeation across the blood-tumor barrier. Herein, we have generated a human NSCLC cell line bearing EGFR exon 19 deletion (PC9) that has been serial passaged in mice to colonize brain (PC9-Br). PC9-Br cells were serially irradiated and allowed to proliferate for 10-14 …