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Small cell lung cancer (SCLC) is among the most aggressive form of lung malignancies and accounts for 15-20% of all lung cancers. It has the tendency to metastasize early, thus limited-stage SCLC patients still receive systemic treatment with chemo-radiotherapy (chemoXRT) for their localized disease. SCLC is exceptionally sensitive to chemoXRT and exhibits high response rates; however, the recurrence rate is > 80% and patients relapse with tumors that resist further treatments. Elucidating mechanisms of chemoXRT resistance in SCLC is needed to develop improved therapies and positively impact patient outcomes.

To better interrogate mechanisms of chemoXRT resistance, we developed a SCLC patient-derived xenograft (PDX) in vivo system for the major molecular subtypes of SCLC (classic and variant). We also established a novel PDX organoid (PDO) model to …