Jean Zhao, PhD

Developing safe and effective therapeutic strategies for treating BRCA1-deficient triple-negative breast cancer.

Impact

Triple-negative breast cancer (TNBC) is an aggressive form of the disease with poor prognoses and limited treatment options. PARP inhibitors have emerged as an effective treatment for TNBC tumors that are driven by mutations in the BRCA1 gene mutation. However, the impact of PARP inhibitors in patients with advanced BRCA-associated TNBC is relatively modest. Dr. Zhao and her colleagues are investigating how an immune suppressive tumor microenvironment promotes resistance to PARP-inhibitors and evaluating strategies to overcome this resistance. Her research will inform the development of more effective therapies which will benefit more patients with this aggressive form of breast cancer.

Progress Thus Far

Dr. Zhao and her team have discovered that BRCA1-mutant breast cancer cells can hijack immune cells called macrophages to support tumor growth. They found that this effect can be blocked by stimulating a factor called STING that reprograms these macrophages to attack tumors. Dr. Zhao and her team have tested this concept in laboratory models of invasive TNBC that are driven in part by the loss of the BRCA1 gene. They found that stimulating STING in these models reduced tumor formation and increased tumor-fighting macrophages.

What’s next

In the coming year, the team will continue their efforts to understand the complex interplay between cancer cells and the immune system. They will use their state-of-the-art models to determine if reprogramming macrophages can prevent the initiation and progression of tumors. They are also interested in how a protein called PI3Kβ contributes to the development of tumors in laboratory models. Their results will provide the key knowledge needed to create additional treatment options for patients with advanced breast cancer harboring key genetic mutations.

“Without the support of BCRF, we would not have been able to uncover these groundbreaking insights into the novel molecular and cellular mechanisms that govern the tumor and its immune microenvironment. These discoveries are pivotal in paving the way for the development of safer and more efficacious treatment strategies for patients with breast cancer.”