Thesis Title: The inflammatory tumor microenvironment as a target in the design of nanoconjugates for the treatment of advanced breast cancer

Author: Paula Soriano Teruel

PhD. Supervisors: Mar Orzáez, Mª Jesús Vicent

Summary:

This thesis focuses on the evaluation of a novel inflammasome inhibitor (MM01) as a chemical tool to study the role of the inflammasome in models of inflammation and cancer.

In this work we delineate a novel mechanism of action for MM01, a recently identified modulator of inflammasome activity. We demonstrate that MM01 disrupts ASC oligomerization, a process associated with the activity of various inflammasomes, and inhibits downstream IL-1β release and death by pyroptosis in various cellular and in vivo models of inflammation. We have employed MM01, to study the role of the inflammasome in tumor progression in different breast cancer models both in vitro and in vivo, and developed a synthetic strategy to obtain a novel nanomedicine that improved the solubility and tumor-targeting capabilities of MM01 in breast cancer.