Recently, a small-scale drug trial conducted in the United States of America made headlines when all its subjects had their rectal cancer go into remission after they were treated with the drug dostarlimab. The research paper was published in the New England Journal of Medicine and detailed that all 12 patients with rectal cancer saw their cancer disappear.
Another medical breakthrough that is making headlines is the discovery of a new compound that has been found to kill a broad spectrum of even the deadliest cancers, including triple-negative breast cancer while bypassing healthy cells. The research, which was carried out in isolated cells on human cancer tissue and on human cancers grown in mice, was published in the journal Nature Cancer.
Dr. Jung-Mo Ahn, a co-corresponding author of the study and a UT Dallas Associate Professor of Chemistry and Biochemistry at the School of Natural Sciences and Mathematics, synthesized a novel compound by exploiting a weakness in cells that had not been targeted by other drugs previously.
For years, he has been designing small molecules that target protein-to-protein interaction in cells and had developed potential therapeutic compounds for treatment-resistant breast cancer and prostate cancer.
ERX-41 Effectively Kills Triple-Negative Breast Cancer Cells
Dr. Jung-Mo Ahn and his colleagues tested the synthesized compound called ERX-41 for its therapeutic effects on breast cancer cells, with and without estrogen receptors (ERs). The novel compound was successful in killing both ER-positive and triple-negative breast cancer (TNBC) cells.
TNBC is known to have the worst outcomes as compared to all other types of breast cancer and has only a few treatment options available. It is more prevalent in women under 40 and lacks receptors for estrogen, progesterone, and human epidermal growth factor 2.
“The ERX-41 compound did not kill healthy cells, but it wiped out tumor cells regardless of whether the cancer cells had estrogen receptors,” Dr. Jung-mo Ahn said.
“In fact, it killed the triple-negative breast cancer cells better than it killed the ER-positive cells,” he added.
Dr. Jung-Mo Ahn explained, “Triple-negative breast cancer is particularly insidious — it targets women at younger ages; it’s aggressive, and it’s treatment-resistant. I’m really glad we’ve discovered something that has the potential to make a significant difference for these patients”.
Targeted Strategy to Kill Cancer Cells
Further research uncovered that ERX-41 binds to a cellular protein called lysosomal acid lipase A (LIPA) which acts as a viable molecular target in TNBC. LIPA is found in a cell structure called the endoplasmic reticulum. By binding to LIPA, ERX-41 blocks the protein processing in the endoplasmic reticulum, which becomes bloated and leads to cell death. Thus, the study implicates a targeted strategy for solid tumors by inducing endoplasmic reticulum stress that resulted in cell death.
It also found ERX-41 to be effective against other types of cancer with elevated endoplasmic reticulum stress, including hard-to-treat pancreatic and ovarian cancers and glioblastoma, as well as the most aggressive primary brain cancer.
When tested, the molecule proved effective in killing human forms of cancerous tumors in mice and cancer cells in human tissue of removed tumors. Moreover, there were no side effects when the team tested the compound in healthy mice. This indicates that the new compound not only effectively kills cancer cells but has no side effects either.
The 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.
The company that was co-founded by Dr. Jung-Mo Ahn and others recently announced that it plans to begin clinical trials with ERX-41 in the first quarter of 2023.