Modeling Epidermal Growth Factor Inhibitor-mediated Enhancement of Photodynamic Therapy Efficacy Using 3D Mesothelioma Cell Culture
Date
2019Journal
Photochemistry and PhotobiologyPublisher
John Wiley & SonsType
Article
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We have demonstrated that lung-sparing surgery with intraoperative photodynamic therapy (PDT) achieves remarkably extended survival for patients with malignant pleural mesothelioma (MPM). Nevertheless, most patients treated using this approach experience local recurrence, so it is essential to identify ways to enhance tumor response. We previously reported that PDT transiently activates EGFR/STAT3 in lung and ovarian cancer cells and inhibiting EGFR via erlotinib can increase PDT sensitivity. Additionally, we have seen higher EGFR expression associating with worse outcomes after Photofrin-mediated PDT for MPM, and the extensive desmoplastic reaction associated with MPM influences tumor phenotype and therapeutic response. Since extracellular matrix (ECM) proteins accrued during stroma development can alter EGF signaling within tumors, we have characterized novel 3D models of MPM to determine their response to erlotinib combined with Photofrin-PDT. Our MPM cell lines formed a range of acinar phenotypes when grown on ECM gels, recapitulating the locally invasive phenotype of MPM in pleura and endothoracic fascia. Using these models, we confirmed that EGFR inhibition increases PDT cytotoxicity. Together with emerging evidence that EGFR inhibition may improve survival of lung cancer patients through immunologic and direct cell killing mechanisms, these results suggest erlotinib-enhanced PDT may significantly improve outcomes for MPM patients. © 2018 The American Society of PhotobiologySponsors
Acknowledgements: This work has been supported in part by NIH/NCI P01-CA087971 and the Penn Translational Centers for Excellence in Mesothelioma Research and Radiation Oncology.Keyword
ErbB Receptors--antagonists & inhibitorsErlotinib Hydrochloride--therapteutic use
Lung
Mesothelioma--therapy
Photochemotherapy
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https://www.scopus.com/inward/record.uri?eid=2-s2.0-85059621854&doi=10.1111%2fphp.13067&partnerID=40&md5=5992c12491c58562b06fde13d1e6d745; http://hdl.handle.net/10713/8635ae974a485f413a2113503eed53cd6c53
10.1111/php.13067
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