Inhibition of EphB4-Ephrin-B2 Signaling Enhances Response to Cetuximab-Radiation Therapy in Head and Neck Cancers

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Shilpa BhatiaSana D Karam

Abstract

Purpose: The clinical success of targeted therapies such as cetuximab and radiotherapy (RT) is hampered by the low response rates and development of therapeutic resistance. In the current study, we investigated the involvement of EphB4-ephrin-B2 protumorigenic signaling in mediating resistance to EGFR inhibition and RT in head and neck cancers.Experimental Design: We used patient-derived xenograft (PDX) models of head and neck squamous cell carcinoma (HNSCC) and HNSCC cell lines to test our hypothesis. Tumor tissues were subjected to PhosphoRTK array, and Western blotting to detect changes in EphB4-ephrin-B2 targets. mRNA sequencing and microarray data analysis were performed on PDX tumors and HNSCC cell lines, respectively, to determine differences in gene expression of molecules involved in tumor cell growth, proliferation, and survival pathways. Effects on cell growth were determined by MTT assay on HNSCC cells downregulated for EphB4/ephrin-B2 expression, with and without EGFR inhibitor and radiation.Results: Our data from locally advanced HNSCC patients treated with standard-of-care definitive chemo-RT show elevated EphB4 and ephrin-B2 levels after failure of treatment. We observed significant response toward cetuximab and...Continue Reading

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Citations

Jun 23, 2020·Molecular Carcinogenesis·Shilpa BhatiaSana D Karam
Apr 27, 2019·Frontiers in Immunology·Simone de LeveVerena Jendrossek
Feb 6, 2020·Journal of Lasers in Medical Sciences·Shabnam ShahrokhMohammadreza Razzaghi
Apr 5, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Shelby LennonSana D Karam
Mar 27, 2019·Current Opinion in Chemical Biology·Marcus Jc LongYimon Aye

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