Abstract

Abstract The objective of this work is to evaluate the effect of individual & combinatorial delivery of Docetaxel (DTX) and Everolimus (EVR) in polymeric micelles at frequent dosing regimen below their maximum tolerated dose on angiogenesis, efficacy & immune signaling in breast cancer animal model. Based on previous in-vivowork in our lab, the maximum tolerated dose (MTDs) for EVR, DTX & combinatorial micelles is 50, 25 and 20 mg/kg respectively. To achieve our goal, two studies have been conducted. First, in-vivo assessment of anti-angiogenic effects of individual & dual DTX-EVR micelles in murine model at 10%, 30%, and 50% MTD, & MTD dose. Second, in-vivo efficacy evaluation of individual & dual DTX EVR micelles at 10%, 30%, 50% MTD, and MTD dose in orthotropic breast cancer murine model. Relative blood vessel invasion & increase in tumor growth will be evaluated for each dosing treatment. We observed that dual DTX EVR polymeric micelles showed significant inhibition of angiogenesis & tumor growth compared to individual agent. The effect of frequent lower dosing schedule is also currently being investigated for its effect immune signaling. Citation Format: Adel Al Fatease, Vidhi Shah, Kalei Lopez, Brianna Cote, Deepa Rao, Adam Alani. Evaluation of combinatorial chemotherapeutics nano-carriers at different dosage regimens in breast cancer model: Tumor immune signaling, inhibit angiogenesis and tumor growth [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 1492.

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