| Literature DB >> 33733072 |
Erdem Bangi1, Peter Smibert1, Andrew V Uzilov2,3, Alexander G Teague1, Sindhura Gopinath1,2, Yevgeniy Antipin2, Rong Chen2,3, Chana Hecht1, Nelson Gruszczynski1, Wesley J Yon1, Denis Malyshev1, Denise Laspina1, Isaiah Selkridge4, Huan Wang3, Jorge Gomez4, John Mascarenhas4,5, Aye S Moe2,3, Chun Yee Lau2,3, Patricia Taik2,3, Chetanya Pandya2, Max Sung4,5, Sara Kim6, Kendra Yum6, Robert Sebra2,3, Michael Donovan7,5, Krzysztof Misiukiewicz4,5, Celina Ang4,5, Eric E Schadt2,3,5, Marshall R Posner4,5, Ross L Cagan1,5.
Abstract
Adenoid cystic carcinoma (ACC) is a rare cancer type that originates in the salivary glands. Tumors commonly invade along nerve tracks in the head and neck, making surgery challenging. Follow-up treatments for recurrence or metastasis including chemotherapy and targeted therapies have shown limited efficacy, emphasizing the need for new therapies. Here, we report a Drosophila-based therapeutic approach for a patient with advanced ACC disease. A patient-specific Drosophila transgenic line was developed to model the five major variants associated with the patient's disease. Robotics-based screening identified a three-drug cocktail-vorinostat, pindolol, tofacitinib-that rescued transgene-mediated lethality in the Drosophila patient-specific line. Patient treatment led to a sustained stabilization and a partial metabolic response of 12 months. Subsequent resistance was associated with new genomic amplifications and deletions. Given the lack of options for patients with ACC, our data suggest that this approach may prove useful for identifying novel therapeutic candidates.Entities:
Keywords: biotechnology; cancer systems biology; genetics; molecular physiology
Year: 2021 PMID： 33733072 PMCID： PMC7940980 DOI： 10.1016/j.isci.2021.102212
Source DB: PubMed Journal: iScience ISSN： 2589-0042