Targeting a vulnerability that has not been discovered before.



Recently, a small group of people with rectal cancer have experienced their disease fade after experimental treatment.

It was a very small experiment by doctors at Memorial Sloan Kettering Cancer Center in New York, where patients took a drug called Dostarlimap for six months. At the end of their trial, each of their tumors disappeared.

Now, in another breakthrough, a new compound manufactured by Dr. Jung Mu Ahn, a researcher at the University of Texas at Dallas, has been found to kill a wide range of difficult-to-treat cancers, including triple negative breast cancer, healthy cells unharmed.

He took advantage of weak cells that were not yet targeted by other drugs.

The study was conducted in isolated cells, in both human cancer tissue and human cancers implanted in mice.

Only a few options for triple negative breast cancer patients

Ahn, a co-author of the study and associate professor of chemistry and biochemistry at UT Dallas at the School of Natural Sciences and Mathematics, has been working on small molecules targeting protein and protein interactions in cells for more than a decade. 

In his current research, Ahn and his colleagues tested a new compound he made called ERX-41 for its effects on breast cancer cells - those containing estrogen receptors (ERs) and those that did not.

Now, there are effective treatments for ER positive breast cancer patients, but there are only a few treatment options for triple negative breast cancer patients (TNBC). Lacks estrogen and progesterone receptors and human skin growth factor 2. TNBC is known to affect women under the age of 40 and have worse results than other types of breast cancer.

There are no adverse effects on healthy mice.

The researchers soon discovered that ERX-41 is associated with lipa, a cellular protein. LIPA was found in a cell structure called the endoplasmic network, a bite that treats and folds proteins.

By linking to LIPA, ERX-41 hinders the processing of protein in the endoplasmic network, which becomes swollen, leading to cell death."The team tested the molecule in healthy mice and noted that there were no bad effects.

"It took us several years to track down the protein that was affected by ERX-41 exactly," Ahn said. That was the hard part. We have chased many dead ends, but we have not given up."I'm really glad we found out something that has the potential to make a big difference to these patients," Ahn said.

You can beat the deadliest cancer.

The researchers then fed mice with human forms of cancerous tumors, and became smaller.

There's more.

They found ERX-41 to be effective against other high-pressure cancers on the endoplasmic network, including pancreatic cancer, difficult-to-treat ovarian cancer and glioblastoma, the most aggressive and deadly type of primary brain cancer.

To investigate the ERX-41 molecule, Ahn worked with collaborators, including collaborating authors, Dr. Janesh Raj, professor of urology and pharmacy at harold C. Simmons Comprehensive Cancer Center at the Southwest Medical Center at the University of Texas, as well as Dr. Ratna Fadlamodi, professor of obstetrics and gynecology at UT Health San Antonio. Dr. Tai Kyung-lee, a former UTD research scientist at the Ahn Organic/Medical Chemistry Laboratory, was also involved in the manufacture of the compound.

Ahn is a joint holder of patents issued and pending on ERX-41 and related vehicles, which were licensed to Dallas startup EtiraRX, a company founded in 2018 by Ahn, Raj and Vadlamudi. The company announced that it plans to start clinical trials on ERX-41 as early as the first quarter of 2023, providing hope for effective new treatments.

Bottom line: Triple negative breast cancer (TNBC) has poor clinical results, due to the lack of actionable treatment goals. Here we identify lipa as a viable molecular target at TNBC and identify a small stereoscopic-level molecule (ERX-41) that binds LIPA. ERX-41 induces endoplasmic network stress (ER) leading to cell death, and this effect on the target as evidenced by specific LIPA mutations that provide resistance. More importantly, we make it clear that ERX-41 activity is independent of lipa lipa function but depends on ER localization. Mechanically, the ERX-41 association with LIPA reduces the expression of many ER-based proteins involved in protein folding. This target gap has a significant therapeutic window, with no negative effects either on normal mammary epithelial cells or in mice. Our study refers to a targeted strategy for solid tumors, including breast, brain, pancreas and ovary, where small molecules are biologically available orally that target lipa block protein folding, cause ER stress and lead to cancer cell death.