Dezheng Huo, PhD, MD

Understanding the disparity in breast cancer incidence and outcomes in women from different ethnic backgrounds.

Impact

Dr. Huo and BCRF collaborator Dr. Funmi Olopade are part of an interdisciplinary team of scientists at the University of Chicago who are focused on expanding treatment and prevention options for women at risk for the most aggressive types of breast cancer. Their BCRF-supported research has focused on dissecting the risk factors and genetic basis of aggressive forms of breast cancer such as estrogen receptor (ER)-negative or triple-negative breast cancer (TNBC). These aggressive cancers disproportionately impact young women of African descent for reasons that are poorly understood. From mechanistic studies examining factors that contribute to the development of aggressive breast cancer in this population, they have identified mutations beyond the well-known cancer predisposition genes BRCA1 and BRCA2. Using a gene editing technology called CRISPR-Cas9, they have focused on how specific genes contribute to aggressive tumor progression. Results of their studies will help to inform the development of more personalized therapies and prevention strategies for patients affected by aggressive breast cancers.

Progress Thus Far

Dr. Huo and his team have identified several pathways that are dysregulated in ER-negative breast cancer as well as several genes that contribute to the progression of aggressive tumors. Their results indicate that one of these genes may play a role in the development of malignant cancer by promoting tumor cell proliferation and resistance to cell death. They have also found that another gene, TRAIL, plays a significant role in regulating immune defense mechanisms and anti-tumor responses in ER-negative breast cancer cells—these functions affect breast cancer initiation and inflammation. They examined how genetic variations in the TRAIL gene might contribute to aggressive types of breast cancer—analysis of these genetic variants is proceeding. Dr. Huo and his colleagues are focusing on another gene regulator of immune response and assessing its role in breast cancer. They found that reducing the expression of the tumor suppressor gene BRCA1P1 (an imperfect version of BRCA1) in breast cancer cell lines and laboratory models can induce antiviral-like activity, stimulate local immunity, and inhibit tumor growth. In the last year, they developed patient-derived organoids to recapitulate the environment of tumors and observed similar outcomes from inhibiting BRCA1P1 function ER-positive lung metastases and TNBC tumors.

What’s next

The team will continue to build organoid biobanks from diverse women with aggressive breast cancers. These provide a particularly attractive and novel tool for conducting initial drug testing in an environment that closely resembles the human breast environment.
They will also build on their studies that suggest BRCA1P1 inhibition could be an efficient way to boost antiviral defense mechanisms across subtypes of breast cancer. His team will continue to explore these findings as an emerging strategy to improve the efficacy of immune-directed therapies.