Tyrosine kinase inhibitor induced growth factor receptor upregulation enhances the efficacy of near-infrared targeted photodynamic therapy in esophageal adenocarcinoma cell lines
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Elmire Hartmans1, Matthijs D. Linssen2, Claire Sikkens1, Afra Levens1, Max J.H. Witjes3, Gooitzen M. van Dam4, Wouter B. Nagengast1
1Department of Gastroenterology and Hepatology, University of Groningen, University Medical Centre, Groningen, The Netherlands
2Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre, Groningen, The Netherlands
3Department of Oral and Maxillofacial Surgery, University of Groningen, University Medical Centre, Groningen, The Netherlands
4Department of Surgery, Nuclear Medicine and Molecular imaging and Intensive Care, University of Groningen, University Medical Centre, Groningen, The Netherlands
Wouter B. Nagengast, email: [email protected]
Keywords: targeted photodynamic therapy, esophageal cancer, epidermal growth factor receptor family (HER-family), targeted treatment
Received: November 02, 2016 Accepted: February 27, 2017 Published: March 13, 2017
Esophageal carcinoma (EC) is a global health problem, with disappointing 5-year survival rates of only 15–25%. Near-infrared targeted photodynamic therapy (NIR-tPDT) is a novel strategy in which cancer-targeted phototoxicity is able to selectively treat malignant cells. In this in vitro report we demonstrate the applicability of antibody-based NIR-tPDT in esophageal adenocarcinoma (EAC), using the phototoxic compounds cetuximab-IRDye700DX and trastuzumab-IRDye700DX, targeting respectively epidermal growth factor receptor 1 (EGFR) and 2 (HER2). Furthermore, we demonstrate that NIR-tPDT can be made more effective by tyrosine kinase inhibitor (TKI) induced growth receptor upregulation. Together, these results unveil a novel strategy for non-invasive EAC treatment, and by pretreatment-induced receptor upregulation its future clinical application may be optimized.
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