Examining EGFR-mediated PI3K/Akt pathway in combination therapy of cetuximab and dynamin inhibition

Adenoid cystic carcinoma (ACC) is a rare and highly aggressive malignant tumor that affects the salivary glands, lacrimal and ceruminous glands of the head and neck region. ACC tends to spread to neighboring regions via perineural methods and metastasize from the primary region to the lung, liver and bones. Current treatment includes surgical resection of the primary lesion followed by radiotherapy. However, about 80% of the patients develop metastatic disease with poor prognosis; hence, new treatment is necessary for ACC patients. EGFR is known to be overexpressed in most of salivary gland carcinomas, particularly ACC. Numerous targeted therapies, including anti-EGFR monoclonal antibody, have been trialed in ACC patients, with disease stabilization reported in approximately half of the trial patients. Our laboratory is examining a combination therapy in which we combined the use of a dynamin inhibitor with monoclonal antibody to enhance antibody-dependent cellular cytotoxicity (ADCC) response in murine models and now in clinical trial. As preclinical data, we examined the signaling profile of the tumor cells in the combination therapy with different dynamin inhibitors. Citation Format: Hui Yi Chew, Benedict Panizza, Caroline Cooper, Riccardo Dolcetti, Jim Coward, Adam McCluskey, Phillip J. Robinson, James W. Wells, Fiona Simpson. Examining EGFR-mediated PI3K/Akt pathway in combination therapy of cetuximab and dynamin inhibition [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr B12.