Progesterone Research Explores New Pathways to Treat Cancer

The idea of using anti-estrogens to treat breast cancer started to take shape in the 1960s, and by the 1970s, Tamoxifen had transformed the field. This revolutionary drug binds to estrogen receptors, preventing estrogen from stimulating the growth of breast cancer cells. By 1977, Tamoxifen received FDA approval for the treatment of metastatic breast cancer. Since then, Tamoxifen has become a cornerstone in early-stage breast cancer care, reducing recurrence and improving survival rates.

“Tamoxifen’s success is built on 75 years of science based on researching the basic biology of estrogen and recognizing its role in breast cancer,” says Christy Hagan, PhD, associate professor of Biochemistry and Molecular Biology. 

Turning to Progesterone

However, when it comes to our understanding of the progesterone hormone, Dr. Hagan adds, we have barely scratched the surface. While progesterone has long been recognized for its role in reproductive health, its impact on cancer progression remains largely uncharted territory. Most breast cancer therapies target estrogen, either by blocking its production or preventing it from activating its receptor. These treatments, such as Tamoxifen, have been effective for many women, but about 30% eventually experience treatment resistance. As a result, the need arises for additional therapies that target different pathways.

Dr. Hagan's research shifts the focus to progesterone, specifically how it helps cancer cells evade the immune system. Now in her 10th year leading her lab at The University of Kansas Cancer Center, Dr. Hagan has played a pivotal role in advancing progesterone and breast cancer research. Her team discovered that progesterone receptors can suppress the danger signals that the immune system needs to detect and remove early tumors. Their work could lead to new therapies that block this interaction, offering hope for those resistant to estrogen-targeted treatments.

 

It is Dr. Hagan’s unique expertise in progesterone research that has led her to look at another type of cancer, uterine endometrial cancer. Rates of endometrial cancer have been on the rise in the United States, and since the mid-2000s, the death rate has increased by 1.7% each year. This type of cancer is typically diagnosed after menopause, though it is increasing in younger women with high estrogen levels. 

Although synthetic progesterone (progestins) is used to counter the effects of excess estrogen in women with endometrial cancer, up to 40% of patients see their cancer return. The goal is to find markers that can predict who will respond to progestin therapy and compare different progestins for their effectiveness and safety, particularly for unwanted growth effects in the breast. Funded by the U.S. Department of Defense and made up of scientists from different institutions across the country, each team member brings specific expertise to the table. 

"I've met many researchers focused on hormone receptors over the years, and the idea to study progesterone and endometrial cancer grew from these connections,” Dr. Hagan says. “It’s a prime example of team science, where experts from all disciplines come together to tackle a complex question.” 

Dr. Hagan believes that expanding progesterone research could reveal crucial insights into how hormonal signals drive not just one, but multiple types of cancer. This cross-cancer approach highlights the potential of progesterone research to influence treatment strategies across different cancers, underscoring the importance of a deeper exploration into this understudied hormone. By broadening the focus beyond breast cancer, Dr. Hagan and her team hope to uncover new biomarkers and therapeutic targets that could revolutionize the way hormonally driven cancers are treated.

“The future of breast cancer research and clinical care is happening right here at KU Cancer Center, and I am thrilled to be part of the movement.,” says Dr. Hagan.