Researchers from two North Texas universities who created a molecule that kills a spectrum of hard-to-treat cancers, including an aggressive form of breast cancer, published their work in Nature Cancer.
The researchers tested the molecule in isolated cells, human cancer tissue, and mice, with a goal to test it in humans by mid-2023, according to the Dallas Morning News. They hope their work could eventually lead to treatments that make a difference in the lives of patients who suffer from these cancers.
“What motivates me now is not just that we understand a particular thing scientifically,” said Jung-Mo Ahn, an associate chemistry professor at the University of Texas at Dallas (UTD) and a co-author of the study. “We realize that this molecule could be very useful and can help other people’s lives.”
Ahn worked on the research with UT Southwestern Medical Center professor Dr. Ganesh Raj and Ratna Vadlamudi from the University of Texas Health Science Center at San Antonio.
In his lab at UTD, Ahn created tiny molecules that can significantly impact how our bodies fight diseases like cancer. He tried 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 (TNBC) is an aggressive form of breast cancer that comprises roughly 15% of new breast cancer diagnoses, according to the Dallas Morning News.
Most breast cancer cells have receptors for hormones like estrogen that scientists can target to kill cancer cells. TNBCs lack those receptors, making chemotherapy one of the only viable treatments.
A few 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 were not expecting it to work on the TNBCs, as they were not 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.
Ahn and his team were determined to find out how their molecule wiped out TNBC cells. Their answer was located in a part of the cell called the “endoplasmic reticulum,” a cellular “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.
Healthy cells have less LIPA than TNBC cells. The researchers found that ERX-41 killed human cancer cells in mice without significantly harming healthy cells.
The idea of killing cancer cells by stressing the endoplasmic reticulum is not new. However, ERX-41 does so by binding to LIPA in a way that is not well-studied.
Ahn said they had found a new way to treat cancer.
“The reason that we think this molecule can be interesting in the end is that we don’t have to worry about too many side effects because we have not seen many side effects,” Ahn told The Dallas Express.
“It doesn’t kill normal cells, but it kills the tumor cells very effectively. That’s why we think this molecule can behave smartly because it targets the things that matter to tumors.”
Juan del Valle, an associate professor at the University of Notre Dame who studies endoplasmic reticulum stress, said Ahn’s research had uncovered both a potential treatment for TNBC and a target within the endoplasmic reticulum that other researchers can study to create new cancer therapies.
“I think what was really fascinating was that it was almost a serendipitous discovery of a new target that might be a viable target for therapeutics in cancer,” said del Valle, who was not involved with the study.
Ahn and his co-authors are working to develop ERX-41 into a treatment that could be tested in animals and eventually human patients. The Dallas-based startup EtiraRX, created by Ahn, Raj, and Vadlamudi in 2018, has licensed the tech with plans to start clinical trials next year.
Since the research was published, Ahn has received phone calls and emails from TNBC patients who have shared their stories with him and encouraged him to continue with the work. Coming from a family of cancer patients, Ahn said the response pushes him forward.
Moreover, his team’s unexpected discovery has been a valuable one.
“Sometimes, life throws a curveball,” Ahn told the Dallas Morning News. “But when you seize the moment… you could actually track it down to the bottom of the pit and then find out there was a treasure waiting to be found.”
