Human Organ Chip Models Recapitulate Orthotopic Lung Cancer Growth, Therapeutic Responses, and Tumor Dormancy In Vitro

• DOI: 10.1016/j.celrep.2017.09.043
• Publication Date: 2017-10-13T04:23:42Z
• Authors: Bryan A. Hassell; Girija Goyal; Esak Lee; Alexandra Sonthei...; Oren Levy; Christopher S. Chen; Donald E. Ingber
• Keywords: ErbB Receptors; Lung Neoplasms; QH301-705.5; Lab-On-A-Chip Devices; Humans; Antineoplastic Agents; Respiratory Mucosa; Biology (General); Proto-Oncogene Proteins c-met; Protein Kinase Inhibitors; Cells, Cultured; Signal Transduction; 3. Good health

Here, we show that microfluidic organ-on-a-chip (organ chip) cell culture technology can be used to create in vitro human orthotopic models of non-small-cell lung cancer (NSCLC) recapitulate organ microenvironment-specific growth, tumor dormancy, and responses tyrosine kinase inhibitor (TKI) therapy observed patients vivo. Use the mechanical actuation functionalities this revealed a previously unknown sensitivity invasion, TKI therapeutic physical cues associated with breathing motions, which appear mediated by changes signaling through epidermal growth factor receptor (EGFR) MET protein kinase. These findings might help explain high level resistance minimal residual disease regions remain functionally aerated mobile, addition providing an experimental model study persister cells mechanisms dormancy vitro.