Even with considerable progress in treatments, breast cancer continues to be a major contributor to cancer-related deaths among women. Typically, management of this disease involves surgery followed by hormone therapy; however, these approaches can lead to long-term issues such as osteoporosis, sexual dysfunction, and blood clots. Researchers have recently introduced an innovative treatment that successfully eliminated small breast tumors and significantly reduced the size of larger ones in mice with just one dose, and it did so without significant adverse effects.
The majority of breast cancers are estrogen receptor positive (ER+), with treatment usually consisting of hormone therapy that spans several years. While these medications tend to cause fewer side effects than chemotherapy, they can still affect the quality of life adversely and pose risks for cancer recurrence and treatment resistance. Consequently, there is a pressing need for cancer therapies that effectively target and kill tumor cells while minimizing side effects.
To tackle this issue, Paul Hergenrother and his team previously created a small molecule known as ErSO. This compound effectively destroys ER+ breast cancer cells, but it is associated with certain negative side effects. In a study released in 2022, the researchers produced a variety of small molecules similar to ErSO, demonstrating that these new derivatives exhibited enhanced potency, better selectivity for ER+ cancer cells, and improved pharmacological characteristics compared to the original compound.
In their most recent research, the team further investigated one of these derivatives, ErSO-TFPy, and discovered that it:
- Effectively killed several human ER+ breast cancer cell lines in lab cultures.
- Showed good tolerance with no apparent adverse effects across multiple species, including mice, rats, and beagles.
- Reduced the size of transplanted human breast tumors with various genetic profiles in mice.
During a dosing study, the researchers observed that a single administration of ErSO-TFPy in mice led to complete or almost complete tumor regression in cases of small or larger tumors, respectively, developed in the animals. Unlike other therapies that necessitate extended dosing periods, the researchers propose that a single dose of ErSO-TFPy, with limited time in circulation within the body, might lower the likelihood of side effects and long-term complications. Although they stress the importance of further testing to validate the drug’s safety and effectiveness, they express optimism that if similar outcomes are seen in human patients, ErSO-TFPy could revolutionize the treatment landscape for ER+ breast cancer.
“It’s quite unusual for a compound to shrink tumors in breast cancer mouse models, let alone fully eliminate them with just one dosage; we are hopeful for the advancement of ErSO-TFPy in breast cancer therapies,” remarks Hergenrother.
The authors acknowledge the support from the National Cancer Institute at the National Institutes of Health and the Cancer Center at Illinois.
