Whole genome sequencing of non-metastatic non-small cell lung cancer primary tumor, patient-derived xenografts and Circulating tumor cells derived xenograft

Circulating tumor cells (CTCs) represent micrometastatic disease and may offer unique insights into future recurrences in lethal malignancies including nonsmall cell lung cancer (NSCLC). Due to CTC rarity and limited stability, no CTC-derived xenograft (CDX) models from non-metastatic NSCLC patients have been generated. Alternative strategies are needed to molecularly characterize CTCs in this potentially curable patient group. Surgically resected NSCLC primary tumor tissues were implanted in immunodeficient mice to establish ten patient-derived xenografts (PDXs). CTCs from 2/10 PDX models led to generation of two stable CDX models that were studied by multi-omics approach involving single cell sequencing, whole genome sequencing (WGS) and proteomics. Drug testings were performed with standard of care chemotherapy (carboplatin/paclitaxel) and a c-MYC inhibitor (10058-F4).