Engineering Bacteria to Treat Breast Cancer

Biomedical Engineer Tal Danino Wins a Department of Defense Era of Hope Scholar Award to Advance his Breast Cancer Research

Ribbon
Breast cancer ribbon created from histology images.  
—Photo courtesy of  Tal Danino/Columbia Engineering

In the US, approximately one in eight women will develop invasive breast cancer at some point in her lifetime, and survival rates drop from 85 to 26 percent when the cancer becomes metastatic and spreads outside of local breast tissue regions. While chemotherapy can stall tumor growth in many cases, tumors often become resistant to treatment. And as treatment options have improved only slightly in the past 20 years, researchers like Tal Danino, assistant professor of biomedical engineering, are determined to develop new methods to treat the disease. Danino’s work on programming probiotics for cancer treatment recently won him the US Department of Defense’s annual Era of Hope Scholar Award, a four-year $2.5 million grant given to young investigators doing innovative breast cancer research.

Danino’s Synthetic Biological Systems Laboratory is using the rapid advances in the field of synthetic biology to engineer probiotics, computationally modeling and then constructing genetic circuits that create complex, dynamic behaviors inside of living cells. Due to the relative ease of genetically manipulating probiotics, his group can program bacteria to sense tumor environments specifically, and produce a wide variety of genetically encoded diagnostic and therapeutic agents.

Before starting at Columbia in 2016, Danino completed postdoctoral training at the Koch Institute for Integrative Cancer Research at MIT. By using small modifications in bacterial genetic circuitry as a leverage point among larger physiological systems, he turned probiotics into a midpoint between liver metastases and a colorimetric urinalysis for cancer detection (Science Translational Medicine), as well as programming probiotics to grow, detonate in-sync, and release a therapeutic cargo upon contact with tumor cells (Nature). Now he is redesigning probiotics to increase safety and efficacy for breast cancer.

“Our work is focused on transforming bacteria into ‘smart’ therapeutic delivery vehicles to treat breast cancer. We think that by engineering microbes that are more effective and less toxic, we can greatly improve upon the mortality associated with metastatic breast cancer,” says Danino. A member of Columbia’s Data Science Institute and Herbert Irving Comprehensive Cancer Center, he studies the interaction of microbes and tumors, using DNA sequences and synthetic biology to program microbes as diagnostics and therapeutics in cancer.

Over the past decade, the human microbiome—all the genomes of the microbes in our bodies—has become a particularly fertile area for cancer researchers, who have found a widespread prevalence of beneficial microbes in the body, including those in breast tissue and human milk. They have also detected a surprising presence of microbes within breast and other tumors previously thought to be sterile. Breast cancer has been associated with imbalances in these diverse communities of breast tissue microbes.

“Given their presence and selectivity for tumors, microbes represent a natural platform for development as a method to treat breast cancer,” Danino says. His DoD award will support his goal to engineer orally deliverable, safe probiotics to selectively target metastatic tumor sites, and effectively produce and release a therapeutic inside the local tumor environment.

Danino envisions a major avenue of breast cancer research that will incorporate an understanding of how the microbiome shapes the development of breast malignancies, and how this microbiome could be manipulated with synthetic biology techniques. In addition, his engineered probiotics can colonize both primary tumors and metastases independent of the patient’s genetic background, a function critical for difficult-to-treat breast cancer subtypes.

“Using orally administered probiotics instead of surgery or chemotherapy could transform treatment regimens,” he notes.

Danino also recently received two other awards related to this work, a DoD Idea Development Award, and the 2017 Breast Cancer Research Foundation-AACR Career Development Award for Translational Breast Cancer Research.

—by Holly Evarts

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