Developin?g a Therapeutics Platform for Adenoid Cystic Carcinoma Summary Adenoid Cystic Carcinoma (ACC) is a rare cancer of the salivary glands. Slow growing, survival rates at 15 years are only 40% due to the relentless nature of the disease. This grant proposal focuses on disease associated with the salivary glands, which accounts for approximately one-third of all reported ACC cases. These tumors typically contain oncogenic C-terminal truncation variants of MYB, most commonly through fusion with NFIB. Importantly, ACC tumors contain other cancer-related genes as well, leading to overall tumor genetic complexity that likely contributes to therapy resistance. Currently, ACC patients have no effective long-term treatment options. In this proposal, we build on our recent clinical experience to develop a novel set of Drosophila ACC transgenic models. Each model is designed to capture a single patient tumor?s genetic complexity. We will then take the first steps towards validating the utility of these fly models by examining whether genetic complexity alters tumor progression and drug response in a whole animal setting. One challenge of the ACC field is the lack of tumor models. This proposal is designed to provide a unique platform that is readily screenable both with genetics and with drug panels.
Developin?g a Therapeutics Platform for Adenoid Cystic Carcinoma Narrative Adenoid Cystic Carcinoma is a rare tumor with a significant mortality profile and few therapeutic options. Based on a recent N-of-1 clinical trial, we propose to develop a set of personalized ?Drosophila patient-matched models? designed to capture the genomic complexity found in ACC patient tumors. We will explore this complexity including identifying drugs and drug cocktails that can reduce transformation.
