Experimental Compound Shows Promise Against Aggressive Breast Cancer

An international research team has published findings on a new experimental compound, DH20931, which slowed the growth of human triple-negative breast cancer tumors in mice without causing noticeable weight loss or signs of toxicity in the animals.

"When that surge goes into the cancer cells, they cannot handle the amount of power they are getting. The fuses burn out, the cell can't handle the surge and it dies."

— Satya Narayan, Ph.D., University of Florida College of Medicine

How the Compound Works

The compound targets the enzyme CerS2, which increases the production of fat-like molecules called ceramides within cancer cells. DH20931 also triggers a surge of calcium into cells. According to the researchers, these combined effects stress and disrupt the mitochondria, the cell's power source, leading to cell death.

In separate laboratory experiments, DH20931 showed activity against other breast cancer subtypes. This broader potential is supported by the compound's mechanism.

"It does not just follow one pathway but it goes through multiple pathways. It's a two-hit hypothesis. These pathways are common in all breast cancer types and other solid tumors, so we think this drug can be useful not only in triple-negative breast cancer but potentially other cancers as well."

— Satya Narayan, Ph.D.

Combination Therapy Potential

A significant finding involved combining DH20931 with the common chemotherapy drug doxorubicin. In lab tests, this combination allowed researchers to use a dose of doxorubicin approximately five times lower than usual to kill cancer cells. This could point to a strategy for reducing chemotherapy side effects.

Furthermore, laboratory tests indicated that healthy cells showed lower sensitivity to DH20931 compared to cancer cells, suggesting a potential therapeutic window.

Background and Publication

Triple-negative breast cancer lacks three common drug targets, which is associated with a more aggressive disease and fewer treatment options. The compound was developed at the University of Florida in the lab of Sukwong Hong, Ph.D.

The study, led by Satya Narayan, Ph.D., a professor at the University of Florida College of Medicine, was published on April 21 in the journal Molecular Cancer Therapeutics. Findings on the combination therapy with doxorubicin were presented at the annual meeting of the American Association for Cancer Research in San Diego.

Next Steps for Research

The researchers noted that while early results are promising, determining the safety and effectiveness of DH20931 as a potential cancer drug for humans would require additional preclinical and clinical trials.