Researchers Discover Promising Compound That Kills Hard-to-Treat Cancer Cells

Scientists from the University of Texas Health Science Center at San Antonio have found a new target for eradicating various hard-to-treat cancer cells in culture and animal models, which could potentially open the door to new drug developments.

According to findings published in Nature Cancer, this new mechanism targets cancer types with high endoplasmic reticulum stress like historically hard-to-treat triple-negative breast cancers (TNBCs).

“We identified a critical vulnerability in multiple cancers and have validated our findings in multiple cancer cell types and animal models,” said study leader Ratna Vadlamudi, PhD, professor of obstetrics and gynecology at UT Health San Antonio, member of the Mays Cancer Center, in a news release. “The range of cell lines and xenografts in which the compound has been shown to work is compelling and indicates that it is targeting a fundamental vulnerability in cancer cells.”

Researchers found that inducing the endoplasmic reticulum, a structured membrane that produces 30% of the human body’s proteins, killed cancer cells.

While the research team examined a compound named ERX-11, which targets estrogen receptors, a protein that fuels most breast cancers, they discovered another compound that rapidly killed TNBCs — ERX-41.

After additional research on ERX-41, the team discovered that ERX-41 was also effective against other types of cancer associated with elevated endoplasmic reticulum stress, including ovarian, pancreatic, and glioblastoma cancers, all of which have limited treatment options.

Because ERX-41 was found to shrink human tumors in mouse models without affecting normal breast cells or causing any observed toxicity, “the safety profile and high therapeutic index of this compound is particularly notable and bodes well for clinical translation,” explained Vadlamudi.

This is promising news for EtiraRx, the Dallas-based startup licensing ERX-41 and planning to transition the drug into clinical trials early next year.

A study published in Nature Communications found that a root protein mechanism associated with neurodegenerative diseases improved when the endoplasmic reticulum was stressed. However, researchers note that stressing out cells may ultimately cause more harm than good.