Hope for the 50% of breast cancer patients resistant to hormonal therapies

Hormonal therapies can be effective in treating breast cancer, but for many, it’s temporary. More than 50 percent develop resistance to the therapy in five years. Dr. Rui Xiong is focused on developing new therapies for that less fortunate half, and it’s working. Dr. Xiong has two therapies in clinical trials. View Halo Profile >>

Tell us about your research…

I am doing early-stage drug discovery for breast cancer. The majority of breast cancer is hormonal receptor (estrogen receptor) driven and is treatable with endocrine therapy; however, at least half of these cancers are refractory or develop resistance to therapy within five years, leaving these patients with only toxic chemo-therapy. I am addressing the problem from three strategic directions – development of selective human estrogen receptor partial agonists (ShERPAs); development of orally bioavailable selective estrogen receptor degraders (SERDs); and development of estrogen-signaling dependent epigenetic vulnerability. 

The majority of breast cancer is hormonal receptor (estrogen receptor) driven and is treatable with endocrine therapy; however, at least half of these cancers are refractory or develop resistance to therapy within five years, leaving these patients with only toxic chemo-therapy

Can you explain that to a non-scientist?

Approximately 70% of all breast cancers are estrogen receptor positive (ER+), where dysregulated ER signaling fuels cancer growth. The standard of care hormonal therapy to treat those patients is either to use estrogen receptor antagonist, tamoxifen, or aromatase inhibitors such as letrozole that block the synthesis of estradiol. More than 50% of patients acquire resistance to these therapy within five years. My research goal is to help those patients that developed resistance to front-line hormonal therapies. We developed novel therapies that can either “stress” estrogen receptor, degrade estrogen receptor, or block estrogen receptor co-regulator proteins. Breast cancer cells without a balanced estrogen receptor signal will stop proliferating.

My research goal is to help those patients that developed resistance to front-line hormonal therapies.

How could it someday impact patient lives?

Two molecules from my research work are currently in phase 1/2 clinical trials and have the potential to become effective therapies for breast cancer patients in a few years.

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