Seema Khan, MD

Investigating the role of the progesterone pathway in breast cancer causation, prevention, and potential treatment.

Impact

Effective preventive measures, including anti-estrogen therapy and surgical removal of the breasts, are available for women who are at high risk of breast cancer or breast cancer recurrence. However, not all women can tolerate anti-estrogen therapy, and others want to keep their breasts. Since the progesterone pathway has been shown to be important in the development and progression of breast cancer, it may be targetable with anti-progesterone medications and may provide an alternative approach to prevent breast cancer. Currently, safety concerns about these medications have precluded their use. Therefore, Dr. Khan and her team are studying new and safer anti-progesterone agents that could improve breast cancer prevention options for high-risk women. They will apply their findings to a new cancer prevention strategy, combining the blockade of both progesterone action and inflammation.

Progress Thus Far

Dr. Khan found that the anti-progesterone drug telapristone decreases tumor formation in a laboratory model, and that the related drug ulipristal acetate (UPA) does the same in a model of BRCA1-deficient breast cancer. Moreover, the preventive effect was related to the suppression of hormone signaling as well as the suppression of inflammation. Laboratory studies found that the combination of UPA plus an anti-inflammatory drug can reduce breast tumor formation and suggests the combination is a promising alternative to single therapies. In parallel, Dr. Khan has engineered and tested a unique drug delivery system, a nanoparticle called Z-ENX-TE. In the last year, her team demonstrated that the delivery system achieved strong drug uptake in breast tissue models with minimal effects to surrounding areas.

What’s next

Dr. Khan will continue to analyze the results of her preclinical studies to optimize the use of novel combinations of UPA and an anti-inflammatory agent in BRCA1-deficient breast cancer. Building on the promising results with the drug delivery system, the team will also expand testing and assess its potential as a safe, localized breast cancer prevention strategy. Dr. Khan and her colleagues hope to validate UPA plus an anti-inflammatory drug as a promising oral preventive therapy, and Z-ENX-TE as a leading candidate for non-invasive drug delivery—results may offer new options for safer, more targeted breast cancer prevention in high-risk women to reduce tumor formation.

Read more about Dr. Khan’s work as part of BCRF’s Precision Prevention Initiative here.