Abstract 2114: Co-delivery nanoparticle to overcome therapeutic resistance in human head and neck cancer promoted by insufficient Src-targeted treatment

Abstract

Head and neck cancer (HNC) exhibiting resistance to molecular-targeted therapeutics poses a challenge to their effective clinical management and alternative treatment strategies are actively sought to improve results. Src is commonly hyperactivated in HNC cells and has been implicated as an oncogenic driver in the development and progression of HNC. Unfortunately, the clinical benefit is dampened significantly in HNC patients because only a small fraction of patients respond positively to Src-targeted treatment, and many develop drug resistance. Here, we demonstrate that the addition of AKT blockade in Src-targeted treatment may prevent activation of alternative signaling pathways to bypass the Src inhibition in HNC cells. The combination of Src and AKT inhibitors significantly suppressed HNC growth more efficiently than either drug alone. However, the properties and pharmacokinetics of two inhibitors required a novel approach to optimal delivery into the same tumor cells. To address this, we developed novel tumor-targeting nanoparticles to selectively co-deliver Src and AKT inhibitors to the tumor site in an orthotopic mouse model of HNC. This nanotherapeutic modality significantly improved the efficacy of tumor repression, which was mainly attributed to the highly specific tumor-targeted drug delivery system and synergistic anticancer effect by co-inactivation of AKT and Src. The results of this study will enable us to take a major step toward addressing the urgent need for single drug resistance and failure, and strongly impact on the development of clinically acceptable therapeutics to combat HNC. Citation Format: Liwei Lang, Chloe Shay, Xuli Wang, Yong Teng. Co-delivery nanoparticle to overcome therapeutic resistance in human head and neck cancer promoted by insufficient Src-targeted treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2114.