DALLAS — Researchers from two North Texas universities have created a molecule that kills a spectrum of hard-to-treat cancers, including an aggressive form of breast cancer. Their work was published in the journal Nature Cancer.
The researchers tested the molecule in isolated cells, human cancer tissue and in mice, with a goal to test in humans by mid-2023. They hope their work could eventually lead to treatments that make a difference in the lives of patients that suffer from these cancers.
“What motivates me now is, it’s not just [that] we understand a particular thing scientifically,” said Jung-Mo Ahn, an associate chemistry professor at the University of Texas at Dallas and an author on the study. “We realize that this molecule could be very useful, and it can help other people’s lives.”
Ahn worked with UT Southwestern Medical Center professor Dr. Ganesh Raj and Ratna Vadlamudi from the University of Texas Health Science Center at San Antonio on the research.
A tale of two elephants
In his lab at UTD, Ahn creates tiny molecules that can have a large impact on how our bodies fight diseases like cancer. He tries to prevent molecular “handshakes” between proteins that lead to uncontrollable cell growth and cancer spread.
“It’s almost like two elephants are hugging each other,” he said, “and you’re throwing a pebble to stop them.”
Triple-negative breast cancer, or TNBC, is an aggressive form of breast cancer that comprises about 15% of new breast cancer diagnoses. Most breast cancer cells have receptors for hormones like estrogen that scientists can target to kill the cancer cells. TNBCs lack those receptors, making chemotherapy one of the only viable treatments.
Several years ago, Ahn’s lab created a tiny molecule that could inhibit protein handshakes in prostate cancers and modified it to work in breast cancers.
The researchers altered the molecule’s structure and tested it on breast cancer cells, using TNBC cells as a baseline. They weren’t expecting it to work on the TNBCs – after all, the molecule wasn’t designed to kill those cells.
When Ahn and his team checked their results, they were surprised. Their molecule had reduced tumor growth in the TNBCs and killed the cancer cells, even though it wasn’t supposed to.
Molecular traffic jams
Ahn and his team were determined to find out how their molecule wiped out TNBC cells. Their answer lurked in a part of the cell called the “endoplasmic reticulum” – a “highway” that guides newly-created proteins to their final cellular destinations.
“What our molecule does is stop the traffic, and stop the highway,” Ahn said.
ERX-41, the molecule Ahn and his team created, binds to a specific protein in the endoplasmic reticulum called LIPA. This causes “traffic jams” in the endoplasmic reticulum, stressing out the cell and initiating its self-destruct protocol.
