New Molecule Discovered Kills Hard-to-Treat Cancers

A team of researchers led by the scientific founders of EtiraRx in Dallas, Texas has identified a small molecule which kills multiple hard-to-treat cancers and could go into clinical tests as early as the first quarter of 2023.

The lab-created molecule, named ERX-41, might be effective against aggressive cancer types with elevated endoplasmic reticulum stress, such as triple-negative breast cancer, pancreatic and ovarian cancers, and glioblastoma, the patent owner company says.

The research was carried out in isolated cells, in human cancer tissue, and in human cancers grown in mice and was published online in June 2022 in the journal Nature Cancer.

The study describing the research explains how ERX-41 kills cancers by exploiting a weakness in cells not previously targeted by other drugs.

Tumor Cells Wiped Out

Dr. Jung-Mo Ahn, a co-corresponding author of the study and a UT Dallas associate professor of chemistry and biochemistry in the School of Natural Sciences and Mathematics, has been designing small molecules that target protein-protein interactions in cells for over a decade, using an approach called structure-based rational drug design.

This time, the novel ERX-41 compound was tested for its effects against breast cancer cells, both those that contain estrogen receptors (ERs) and those that do not.

While there are effective treatments available for patients with ER-positive breast cancer, there are few treatment options for patients with triple-negative breast cancer (TNBC), which generally affects women under forty and has poorer outcomes than other types of breast cancer, an article by the University of Texas explains.

The researchers fed the compound to mice with human forms of cancerous tumors, and the tumors shrunk. It also killed cancer cells in human tissue gathered from patients who had their tumors removed.

“The ERX-41 compound did not kill healthy cells, but it wiped out tumor cells regardless of whether the cancer cells had estrogen receptors,” Ahn commented.

“In fact, it killed the triple-negative breast cancer cells better than it killed the ER-positive cells. I’m really glad we’ve discovered something that has the potential to make a significant difference for these patients,” he added.

Innovative Treatment for Aggressive Cancers

Ahn’s research on this project is supported by the National Cancer Institute, part of the National Institutes of Health; the Cancer Prevention and Research Institute of Texas; and The Welch Foundation.

Co-corresponding authors Dr. Ganesh Raj, professor of urology and pharmacology at the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern Medical Center, and Dr. Ratna Vadlamudi, professor of obstetrics and gynecology at UT Health San Antonio, as well as Dr. Tae-Kyung Lee, a former UTD research scientist in Ahn’s Bio-Organic/Medicinal Chemistry Lab, were also involved in synthesizing the treatment compound.

“These discoveries are exciting as they represent a novel approach to targeting the Achilles heel of many aggressive cancers: their vulnerability to enhanced ER stress,” Dr. Raj said.

He added that the “critical finding was that of a new therapeutic target (LIPA) and its undiscovered role in protein folding. By targeting LIPA with ERX-41, protein folding in the cancer cell was disrupted, causing ER stress and promoting cancer cell death.”

Findings indicate the potential for an effective oral treatment for patients with aggressive cancers for whom options are limited, the researcher concluded.

Dallas-based startup EtiraRx, co-founded by Ahn, Raj, and Vadlamudi in 2018, is underway completing necessary preclinical studies and plans to initiate clinical trials with the novel compound in the first quarter of 2023.

Russell Hayward, CEO EtiraRx, said, “ERX-41 has the potential to be a first-in-class oral therapy that kills aggressive therapy-resistant cancers. We are committed to moving these drugs forward to clinical trials and [making] a difference in the lives of patients with lethal cancers.”