A novel drug candidate developed by researchers at the University of Illinois called ErSO-TFPy, has demonstrated the ability to completely eliminate breast cancer tumors in mice with a single dose. The new compound, detailed in a study published in ACS Central Science, offers the potential to be developed as a more effective treatment for estrogen receptor-positive (ER+) breast cancer, a prevalent and difficult-to-treat form of the disease.
Paul Hergenrother, PhD, lead researcher of the study and a professor of chemistry at the University of Illinois, expressed enthusiasm about the breakthrough, stating, “It is very rare for a compound to shrink tumors in mouse models of breast cancer, let alone completely eradicate those tumors with a single dose, so we are eager for ErSO-TFPy to advance for treatment of breast cancer.”
Approximately 70% of breast cancers are ER+ and are typically for several years with hormone therapy. While these treatments are better tolerated than chemotherapy, hormone therapy has been shown to have a number of long-term deleterious health implications such as osteoporosis, blood clots, and sexual dysfunction. Medication adherence can also be an issue as treatments are taken daily and patients often lapse in their medication plans. Given these issues, the development of more effective and less cumbersome treatments for ER+ breast cancer could significantly improve long-term patient outcomes.
For this study, the researchers tested a modified derivative of a previously developed small molecule, ErSO, which had shown potential for treating ER+ breast cancer but also produced undesirable side effects. ErSO-TFPy, however, was found to be more potent and selective in targeting ER+ cells while causing fewer harmful side effects.
The new compound effectively killed multiple human ER+ breast cancer cell lines in laboratory conditions and was shown to be well-tolerated in mice, rats, and beagles. In the mouse model, a single intravenous dose of ErSO-TFPy resulted in the regression of tumors that were either small or large, with the larger tumors showing a reduction of more than 80%. Such response rates for a new cancer treatment, even one that is still in preclinical stages, is quite rare. Further, small molecule treatments typically are administered with multiple rounds of frequent dosing.
A regimen that consists of a single dose would significantly change the face of ER+ breast cancer treatment. “A single dose, or a handful of doses, could change the face of breast cancer treatment,” the researchers wrote. “Currently, even optimized drugs targeting the estrogen receptor fail to induce dramatic tumor regression when used alone. ErSO-TFPy’s effectiveness in a single dose is exceptional.” The researchers noted that while some immunotherapies like CAR-T have shown single-dose efficacy, they are complex and expensive and have not yet proven effective for ER+ breast cancer.
Additional studies will be necessary to confirm the compound’s safety, long-term efficacy, and potential side effects. Notably, while the drug has shown to be well-tolerated in animals, its effects on the immune system remain unclear. However the investigators said it’s possible the compound could activate immune responses, which could enhance its effectiveness and help prevent the development of treatment resistance.
In addition to its continued work in breast cancer, the team also plans to study whether ErSO-TFPy might be effective against other cancers, such as colorectal and prostate cancer, where similar estrogen-related pathways are involved.
“These studies also provide an unusual case study of pharmacokinetics, where the short exposure times in the blood of mice do not limit ErSO-TFPy from initiating tumor cell death,” the researchers said. “If translated to humans, this compound would provide a significant clinical benefit.”
