Abstract
Abstract Lacrimal gland adenoid cystic carcinoma is a rare but highly lethal indolent cancer originating in the cells of secretory glands, primarily of the head and neck. With the 10-year survival rate of 20%, the only life extending technique is to remove the eye and surrounding socket contents entirely. Despite radical treatment, ACC is a very slow growing tumor and most patients will present with metastatic disease to the brain, lung, liver, or bones several years out from initial diagnosis and before symptoms are noticeable. Due to the rarity of LGACC, it is not well understood, but extensive genome analysis of ACC of the head and neck has previously uncovered a high mutation rate of MYB and NOTCH in patient samples, though unfortunately neither can be directly targeted by drugs. We have RNA sequencing data for 7 primary LGACC tumors, mass spectrometry data for 12 primary tumors and RNA sequencing for 15 cell lines derived from tumors to discover possible targetable biomarkers in LGACC and to further understand the biology of these tumors. Our analysis has revealed the signatures and drivers of LGACC, most significantly involving extracellular matrix mechanisms including HAPLN1, FABP7, and VCAN. We compared the genes of proteins differentially expressed in the mass spectrometry and RNA sequencing data and discovered 194 genes that were differentially expressed in both analysis types. With this extensive understanding of the molecular signatures, we used iLINCS integrated web-based platform to determine compounds that would target the differentially expressed genes. We have selected compounds based on a rubric we generated and will test them individually and in combination on LGACC cell lines to determine the best specific treatment for primary tumors and metastatic disease. Citation Format: Acadia H. Moeyersoms, Vasileios Stathias, Michelle Zhang, Ryan A. Gallo, David T. Tse, Daniel Pelaez. Discovering novel targets for adenoid cystic carcinoma of the lacrimal gland [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2147.