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429 Eribulin Synergizes with STING Agonists by Enhancing Type 1 Interferon Expression and Improves Antitumor Efficacy as Combination Treatment by Takahashi-Ruiz, Leila (author);Fermaintt, Charles S. (author);Wilkinson, Nancy (author);Chan, Peter Y. (author);Mooberry, Susan L. (author);Risinger, April L. (author) is a Medicine article available to read on EtoBox.

What is 429 Eribulin Synergizes with STING Agonists by Enhancing Type 1 Interferon Expression and Improves Antitumor Efficacy as Combination Treatment about?

OBJECTIVES/GOALS: Triple-negative breast cancer (TNBC) is a subtype of breast cancer that lacks effective targeted treatment options. TNBC's greater degree of immunogenicity than other breast tumors makes immunotherapy a viable strategy. Strategies to improve the immunotherapy response includes targeting the cGAS-STING innate immune pathway with STING agonists. METHODS/STUDY POPULATION: We have previously shown in vitro that eribulin, a microtubule destabilizer currently used in the treatment of TNBC, functions as an indirect STING agonist because it promotes the release of mitochondrial DNA into the cytoplasm. Separately, eribulin also significantly enhances type I interferon expression induced by STING agonists measured by qRT-PCR through a second TBK1-dependent mechanism downstream of STING activation through detecting higher amounts of phosphorylated IRF-3 by western blot protein analysis. Mechanisms of eribulin-mediated interferon expression occur in immune and TNBC cells and are shared with other microtubule destabilizers but not with the microtubule stabilizing agent paclitaxel. RESULTS/ANTICIPATED RESULTS: We determine that the enhancement of type I interferon expression by

Who reads 429 Eribulin Synergizes with STING Agonists by Enhancing Type 1 Interferon Expression and Improves Antitumor Efficacy as Combination Treatment?

Author

Takahashi-Ruiz, Leila (author);Fermaintt, Charles S. (author);Wilkinson, Nancy (author);Chan, Peter Y. (author);Mooberry, Susan L. (author);Risinger, April L. (author)

Publisher

Cambridge University Press (CUP)

Published

2023

Language

EN

Field

Medicine (Health Sciences)