A limitation of patient-derived xenograft (PDX) models is they do not develop metastases. To address this limitation, while still preserving the use of patient-derived cancer tissue, we developed a LUAD patient-derived organoid (PDO) platform. All PDOs are clinically and genomically (MSK-IMPACT) annotated. Preservation of histologic architecture and concordant genomic and transcriptomic profiles between the primary tumor and corresponding PDO were confirmed by our pathologists and WGS & RNA-seq, respectively. To explore if LUAD PDOs possess metastatic potential, we have developed a PDO intracardiac injection metastatic model, which allows us to examine the metastatic capabilities of PDOs to different organs. Utilizing our PDO platform, we are particularly interested in exploring how tumor genetic alterations and the perturbation of the chromatin landscape contribute to tumorigenesis and metastases of LUAD. Finally, using PDOs and PBMCs from the same patient we are examining the immune priming capabilities of sensitizing chemotherapy or radiation to PD-1 inhibitors and its impact on tumor cell death. Collectively, this platform allows us to leverage the power of PDOs in examining LUAD metastases in vivo, as well as exploring therapeutic vulnerabilities, including immune-priming strategies for individual patient tumors. We collaborate with the MSKCC Center for Molecular Oncology, Animal Imaging, IGO, Anti-Tumor Assessment, and Pathology.