Gaorav Gupta, MD, PhD

Understanding the effects of gene mutations on the immune response to breast cancer.

Impact

Breast cancer remains a prevalent health concern, with a critical need to understand how it develops from early, non-invasive stages to invasive and aggressive tumors. Dr. Gupta’s research aims to explore how the immune system interacts with precancerous cells in the breast, focusing on key mechanisms that could help prevent the progression to full-blown cancer. This study has the potential to inform new strategies for early detection, prevention, and improved breast cancer treatments

Progress Thus Far

In their first year of BCRF funding, Dr. Gupta’s team uncovered important insights into how the immune system interacts with early breast cancer and how aggressive cancers adapt to DNA damage. By analyzing individual immune cells in a model of triple negative breast cancer (TNBC), the team identified specific alterations in the immune microenvironment during tumor progression. At the same time, they studied the DNA damage response in TNBC cells and found that loss of a gene called FANCA creates a unique weakness that makes cancer cells highly sensitive to PARP inhibitors, which work by targeting DNA repair. They confirmed this vulnerability across multiple models and revealed new details about how FANCA functions in DNA repair. These results give insight into how breast cancers evade immune surveillance and adapt to stress and may provide a new therapeutic target.

What’s Next

Dr. Gupta and his team will build on their work investigating how DNA damage sensing in tumor cells influences immune surveillance at the earliest stages of breast cancer. Using advanced single-cell sequencing, the team aims to track T cell responses over time and test whether stimulating the STING pathway—a key part of the innate immune system—can enhance immune recognition of precancerous lesions. In parallel, the team is analyzing samples from the P-RAD clinical trial, which is testing radiation combined with immunotherapy as a way to “prime” breast tumors for better responses to standard treatment. Finally, they are probing the role of necroptosis—a form of cell death—in driving immune responses to combined radiation and immunotherapy. Dr. Gupta’s research so far suggests that this process helps alert and activate immune cells in ways that could be harnessed for new treatments.