Bangi, E., Smibert, P., Uzilov, A.V., Teague, A.G., Gopinath, S., Antipin, Y., Chen, R., Hecht, C., Gruszczynski, N., Yon, W.J., Malyshev, D., Laspina, D., Selkridge, I., Wang, H., Gomez, J., Mascarenhas, J., Moe, A.S., Lau, C.Y., Taik, P., Pandya, C., Sung, M., Kim, S., Yum, K., Sebra, R., Donovan, M., Misiukiewicz, K., Ang, C., Schadt, E.E., Posner, M.R., Cagan, R.L. (2021). A Drosophila platform identifies a novel, personalized therapy for a patient with adenoid cystic carcinoma.  iScience 24(3): 102212.

FBrf0248488

Research paper

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.

PMC7940980 (PMC) (EuropePMC)