Drug candidate eliminates breast cancer tumors in mice in a single dose

Despite significant therapeutic advances, breast cancer remains one of the leading causes of cancer death among women. Treatment usually involves surgery and follow-up hormone therapy, but late effects of these treatments include osteoporosis, sexual dysfunction, and blood clots.

Today, researchers report in ACS Central Science have created a new treatment that eliminates small breast tumors and significantly shrinks large tumors in mice in a single dose, without problematic side effects.

Most breast cancers are estrogen receptor positive (ER+) and treatment usually involves several years of hormone therapy. Although these medications are better tolerated than chemotherapy, they still cause side effects that decrease quality of life and can put people at risk of cancer recurrence and resistance to treatment. There is therefore a need for anticancer drugs that kill tumor cells selectively and aggressively, while limiting side effects.

To address this challenge, Paul Hergenrother and his colleagues previously developed a small molecule called ErSO. This compound kills ER+ breast cancer cells but causes unwanted side effects.

In 2022, researchers synthesized a series of small molecules similar to ErSO. This previous study demonstrated that these derivatives have higher potency, greater selectivity for ER+ cancer cells, and better pharmacological properties than the parent compound.

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

• Effectively kills multiple ER+ human breast cancer cell lines in culture.
• Was well tolerated, without obvious deleterious effects, by several species (mice, rats and beagles).
• Reduces transplanted human breast tumors of various genetic backgrounds in mice.

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 that had developed in the animals, respectively.

Other medications require long-term dosing, but researchers suggest that a single 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 the safety and effectiveness of the drugs, but suggest that if these results translate to human patients, ErSO-TFPy could be transformative for the treatment of ER+ breast cancer .

“It is very rare for a compound to shrink tumors in mouse models of breast cancer, let alone completely eradicate these tumors with a single dose. So we look forward to seeing ErSO-TFPy advance in the treatment of breast cancer “, says Hergenrother.