Breakthrough Single-Dose Drug Wipes Out Breast Tumors in Mice Without Side Effects

A revolutionary new treatment for breast cancer has shown the ability to eliminate small breast tumors and significantly shrink large ones in mice with a single dose.

This innovative approach targets estrogen receptor-positive cancers more selectively, aiming to reduce side effects and improve patient outcomes.

New Breast Cancer Treatment Research

Despite advances in treatment, breast cancer remains one of the leading causes of cancer-related deaths among women. Standard treatment usually includes surgery followed by hormone therapy. However, these treatments can have long-term side effects, such as osteoporosis, sexual dysfunction, and blood clots. Researchers publishing today (January 22) in ACS Central Science have now developed a new treatment that, in a single dose, eliminated small breast tumors and significantly reduced larger ones in mice—all without harmful side effects.

Current Limitations in Hormone Therapy

The majority of breast cancers are estrogen receptor-positive (ER+), meaning they rely on estrogen to grow. Current treatment often requires several years of hormone therapy, which, although generally more tolerable than chemotherapy, can still lead to significant side effects that impact quality of life. Additionally, these treatments do not eliminate the risk of cancer recurrence or resistance. This highlights the urgent need for therapies that can effectively target and destroy cancer cells while minimizing adverse effects.

Development of a Promising Molecule

To address this challenge, Paul Hergenrother and colleagues previously developed a small molecule called ErSO. This compound kills ER+ breast cancer cells but results in undesirable side effects. In 2022, the researchers synthesized a series of small molecules similar to ErSO. That prior study demonstrated that these derivatives have higher potency, greater selectivity for ER+ cancer cells and better pharmacological properties than the original compound.

Breakthrough Findings with ErSO-TFPy

Now, in the latest study, the researchers further evaluated one derivative, ErSO-TFPy, and found that it:

• Effectively killed multiple human ER+ breast cancer cell lines in culture.
• Was well tolerated, with no obvious deleterious effects, by multiple species (mice, rats and beagles).
• Shrank transplanted human breast tumors of various genetic backgrounds in mice.

Potential for Transformative Cancer Treatment

In a dosing experiment, the researchers noted that a single dose of ErSO-TFPy in mice induced complete or near-complete regression of small or large tumors, respectively, that had grown in the animals. Other drugs require long-term dosing, but the researchers suggest that a lone dose of ErSO-TFPy and therefore minimal circulation in the body could help reduce the risk of side effects and late effects. They acknowledge the need for more testing to confirm drug safety and efficacy, but they suggest if these results translate to human patients, ErSO-TFPy could be transformative for ER+ breast cancer treatment.

“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,” says Hergenrother.

Reference: “Single Dose of a Small Molecule Leads to Complete Regressions of Large Breast Tumors in Mice” by Michael P. Mulligan, Matthew W. Boudreau, Brooke A. Bouwens, Yoongyeong Lee, Hunter W. Carrell, Junyao Zhu, Spyro Mousses, David J. Shapiro, Erik R. Nelson, Timothy M. Fan and Paul J. Hergenrother, 22 January 2025, ACS Central Science.
DOI: 10.1021/acscentsci.4c01628

The authors acknowledge funding from the National Cancer Institute at the National Institutes of Health and the Cancer Center at Illinois.

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