Microbiome research has revealed the widespread prevalence of beneficial probiotic bacteria within the human body, and surprisingly the presence of bacteria within breast tumors. At the same time, several studies have demonstrated that the administration of probiotic bacteria either orally or intravenously results in selective colonization of tumor environments. Given their presence and preference for tumors, probiotic bacteria present an opportunity as a natural platform for development as “smart” delivery vehicles for breast cancer.

In this proposal, we will use novel approaches from synthetic biology to genetically program probiotics to safely produce and deliver therapeutics. We will do so by developing an engineering framework that bridges in silico mathematical modeling, novel in vitro experimental technologies, and mouse cancer testing in vivo. We will focus our probiotic therapies on primary and metastatic breast cancer, developing therapeutics that deliver drugs locally to tumor environments for enhanced safety and efficacy. This proposal primarily focuses on the overarching challenge to revolutionize treatment regimens by replacing them with ones that are more effective and less toxic, along with eliminating mortality associated with metastatic breast cancer. The ultimate objective is to develop a translatable probiotic to be used alone or in combination with other breast cancer therapeutics. We expect that the work developed in this proposal will narrow down candidates for further preclinical development and clinical trials, and in turn improved patient outcomes.