01675nas a2200229   4500000000100000000000100001008004000002260001200042100002100054700001700075700001300092700003200105700001400137700002400151700002100175245012300196856006700319300001200386490000700398520102700405022001301432       10                             d  c10/20171 aBryan A. Hassell1 aGirija Goyal1 aEsak Lee1 aAlexandra Sontheimer-Phelps1 aOren Levy1 aChristopher S. Chen1 aDonald E. Ingber00aHuman Organ Chip Models Recapitulate Orthotopic Lung Cancer Growth, Therapeutic Responses, and Tumor Dormancy In Vitro  uhttps://linkinghub.elsevier.com/retrieve/pii/S2211124717313311  a508-5160 v213 aHere, we show that microfluidic organ-on-a-chip (organ chip) cell culture technology can be used to create in vitro human orthotopic models of nonsmall-cell lung cancer (NSCLC) that recapitulate organ microenvironment-specific cancer growth, tumor dormancy, and responses to tyrosine kinase inhibitor (TKI) therapy observed in human patients in vivo. Use of the mechanical actuation functionalities of this technology revealed a previously unknown sensitivity of lung cancer cell growth, invasion, and TKI therapeutic responses to physical cues associated with breathing motions, which appear to be mediated by changes in signaling through epidermal growth factor receptor (EGFR) and MET protein kinase. These findings might help to explain the high level of resistance to therapy in cancer patients with minimal residual disease in regions of the lung that remain functionally aerated and mobile, in addition to providing an experimental model to study cancer persister cells and mechanisms of tumor dormancy in vitro.  a22111247