Despite significant advances in targeted therapies for lung cancer, nearly all patients develop drug resistance within 6-12 months and prognosis remains poor. Developing drug resistance is a progressive process that involves tumor cells and their microenvironment. We hypothesize that microenvironment factors alter tumor growth and response to targeted therapy. We conducted in vitro studies in human EGFR-mutant lung carcinoma cells, and demonstrated that factors secreted from lung fibroblasts results in increased tumor cell survival during targeted therapy with EGFR inhibitor, gefitinib. We also demonstrated that increased environment stiffness results in increased tumor survival during gefitinib therapy. In order to test our hypothesis in vivo, we developed a multimodal optical imaging protocol for preclinical intravital imaging in mouse models to assess tumor and its microenvironment over time. We have successfully conducted multimodal imaging of dorsal skinfold chamber (DSC) window mice implanted with GFP-labeled human EGFR mutant lung carcinoma cells and visualized changes in tumor development and microenvironment facets over time. Multimodal imaging included structural OCT to assess tumor viability and necrosis, polarization-sensitive OCT to measure tissue birefringence for collagen/fibroblast detection, and Doppler OCT to assess tumor vasculature. Confocal imaging was also performed for high-resolution visualization of EGFR-mutant lung cancer cells labeled with GFP, and was coregistered with OCT. Our results demonstrated that stromal support and vascular growth are essential to tumor progression. Multimodal imaging is a useful tool to assess tumor and its microenvironment over time.
Lida P. Hariri, Matthew J. Niederst, Hillary Mulvey, David C. Adams, Haichuan Hu, Isabel Chico Calero, Margit V. Szabari, Benjamin J. Vakoc, Tayyaba Hasan, Brett E. Bouma, Jeffrey A. Engelman, and Melissa J. Suter, "Multimodal imaging of lung cancer and its microenvironment (Conference Presentation)," Proc. SPIE 9691, Endoscopic Microscopy XI; and Optical Techniques in Pulmonary Medicine III, 96911F (Presented at SPIE BiOS: February 14, 2016; Published: 27 April 2016); https://doi.org/10.1117/12.2214658.4828146976001.
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