New mechanism behind biotech's estrogen-targeting breast cancer drug opens the door for other hard-to-treat cancers

Scientists have discovered a new target for killing off a variety of hard-to-treat cancer cells, opening the door for potential new drugs—an opening that biotech EtiraRx has already lodged its foot in.

The new mechanism is targeting cancer types with high endoplasmic reticulum stress, such as triple-negative breast cancers (TNBCs), which are historically difficult to treat, according to findings published June 2 in Nature Cancer. Researchers discovered that inducing the endoplasmic reticulum—a membrane structure that produces 30% of the body’s proteins—killed off cancer cells.

At first, study lead Ratna Vadlamudi, Ph.D., professor of obstetrics and gynecology at UT Health San Antonio and member of the Mays Cancer Center, and colleagues set out to examine a compound called ERX-11, which targets the estrogen receptor, a protein that fuels most breast cancers. During that work, the researchers discovered that another compound—ERX-41—quickly killed TNBCs. The cancer type is associated with poor clinical outcomes.

The researchers then expanded their studies and found ERX-41 was also effective against other cancer types with elevated endoplasmic reticulum stress, such as pancreatic, glioblastoma and ovarian cancers—all of which have limited treatment options.   

What’s more—ERX-41 shrunk the human tumors grown in mouse models without affecting normal breast cells or causing any observed toxicity. The safety profile and high therapeutic index bodes well for the drug’s transition to clinic, Vadlamudi said in a news release.

Which is good news for EtiraRx, a Dallas-based startup that is licensing ERX-41. The biotech aims to move the drugs into clinical trials early next year.  

This isn’t the only recent research to zoom in on the endoplasmic reticulum. Findings published in May discovered that when the endoplasmic reticulum was stressed, a root protein mechanism tied to neurodegenerative diseases actually improved. However, though it may still present a potential therapeutic avenue, the researchers noted that stressing out cells may ultimately cause more harm than good.