New drug candidate "shreds" cancer-causing protein in early lab tests
Researchers in Germany have developed a new drug that can act like a “shredder” for proteins implicated in causing cancer. In tests on lab-grown cancer cells, the drug worked to kill the tumors, suggesting a new pathway to a treatment for the disease.
In higher-than-usual amounts, some proteins have been linked to an increased risk of cancer, and Aurora-A kinase (or just Aurora) has long been known to be among them. This protein is overexpressed in some breast and prostate cancers, leukemias and neuroblastomas, among others.
Inhibiting these “tumorigenic” proteins is one avenue of cancer treatment that scientists are exploring. But usually drugs just shut down the proteins without destroying them, which helps fight the tumor but doesn’t stop the proteins’ functions entirely. Unfortunately, these kinds of drugs haven’t yet proven too effective in tests.
“Aurora-A kinase is present in much higher concentrations in many cancer tissues than in healthy tissue and it also plays a key role in prostate cancer,” says Stefan Knapp, an author of the study. “Blocking the activity of Aurora-A kinase alone seems not a promising approach as none of the many clinically tested drug candidates has achieved clinical approval.”
In the new study, researchers at Würzburg and Frankfurt Universities developed a class of experimental drugs called PROTACs, which degrade select proteins completely. And one PROTAC was found to be very effective against Aurora-A kinase specifically.
“The tumor needs certain tumor-promoting proteins, which we can imagine as the pages of a book,” says Elmar Wolf, an author of the study. “Our PROTAC substance tears out the ‘Aurora’ pages and destroys them with the help of the machinery that every cell has to degrade old and broken proteins.”
In tests on cancer cell lines grown in the lab, the PROTAC worked to degrade the Aurora proteins of the tumors, resulting in cell death.
The initial results are intriguing, but of course it’s still very early days for this research. The next steps for the team will be to test how effective and well-tolerated the treatment might be in animals, before it can even be considered for human trials.
The research was published in the journal Nature Chemical Biology.
Source: Würzburg University