Lung cancer is the leading cause of cancer-related deaths in the United States, with the main driver being metastatic disease. The skeletal system is a frequent site of metastasis from lung cancer and other solid tumors, and causes major clinical challenges including pain, pathologic fractures, cord compression, and treatment resistance. My research focuses on developing patient-specific tumor-on-chip models incorporating human tumor microenvironments (TME) to evaluate novel drug therapies and predictive biomarkers in lung cancer, with an emphasis on studying the TME in bone metastases. We use patient-derived cancer organoids (PDCOs), human primary stromal cells, and cancer cell lines in 3D microfluidic devices to investigate how bone stromal cells affect functional and molecular responses to targeted drug therapies. To interrogate whether findings in our chip can translate to clinical use, we employ a semi-automated circulating tumor cell (CTC) enrichment platform to assess global molecular changes, identify tumor heterogeneity, and advance biomarker discovery in lung cancer.  Our overall goal is to identify stromal-mediated mechanisms of resistance and develop new strategies to address treatment-refractory lung cancer.