A researcher at the University of Texas at Dallas has created a molecule that kills a wide range of hard-to-treat cancers by exploiting a weakness in cells not previously targeted by other drugs.
A study describing the research, which was carried out in isolated cells, in human cancer tissue and in human cancer grown in mice, was published online June 2.
Dr. Jung-Mo Ahn is an associate professor of chemistry and biochemistry in the School of Natural Sciences and Mathematics at UT Dallas, and he has been passionate about his work for over a decade. He used a structure-based rational drug design approach to develop potential therapeutic candidate compounds.
Ahn and his colleagues tested a novel compound he created for its effects against breast cancer cells, both those with and without ERs, as well as those that do not. There are effective treatments for patients with ER-positive breast cancer, but there are not many options for patients with triple- negative breast cancer. Women under 40 are more likely to be affected by TNBC than other types of breast cancer.
The compound did not kill healthy cells, but it wiped out the tumors. It killed triple-negative breast cancer cells more effectively than the ER-positive cells.
At the time, it was baffling to us. We knew it was targeting something other than the TNBC cells, but we had no idea what that was.
Dr. Ratna Vadlamudi and Dr. Ganesh Raj are co-corresponding authors of the study. The compound was synthesised by a former UTD research scientist.
The lysosomal acid lipase A is found in the cell. The endoplasmic reticulum is an organelle that processes and folds cells.
Ahn said that stress on the endoplasmic reticulum is what causes tumors to grow quickly. LIPA is overproduced by cancer cells more than healthy cells. The binding of ERX41 to LIPA jams the function of the reticulum which leads to cell death.
There were no adverse effects when the compound was tested in mice.
It took us a long time to find out which part of the body was affected by ERX41. That was the challenge. Ahn said that they did not give up.
Triple-negative breast cancer targets women at younger ages and is resistant to treatment. I'm happy that we've found a way to help these patients.
The compound was fed to mice and they got smaller tumors. The molecule was able to kill cancer cells in tissue from patients who had their tumors removed.
Pancreatic and ovarian cancers, and the most aggressive and lethal primary brain cancer, are some of the cancer types that ERX 41 is effective against.
"As a chemist, I am somewhat isolated from patients, so this success is an opportunity for me to feel like what I do can be useful to society."
Ahn, Raj and Vadlamudi are the co-owners of the Dallas-based startup EtiraRX, which has been granted a license by Ahn, Raj and Vadlamudi. According to the company, it will begin clinical trials of ERX-41 in the first quarter of 2020.
The National Cancer Institute, part of the National Institutes of Health, is one of the funders of Ahn's research.
Other study authors included from Howard Hughes Medical Institute's Janelia Research Campus, Northwest A&F University in China, and the Medical College of Xiamen University in China.
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