Molecular biologists in the School of Medicine at The University of Texas Health Science Center San Antonio have found a novel way to fine-tune the activity of cells’ protein-disposing machinery, with potentially cancer-fighting effects.
This machinery, the proteasome, is deregulated in cancer. Agents called protease inhibitors are viewed as potential anti-cancer therapies, but they indiscriminately curb proteasome activity, which also includes protein recycling. Such strategy is effective to kill cells in aggressive blood cancers but leads to drug resistance and excessive toxicity in solid tumors.
Fine-tuning
The new strategy may change that. By basically outsmarting the cell’s machinery, compounds called allosteric regulators are able to fine-tune the proteasome actions instead of block them. “The result is that cell lines from solid tumors, which are resistant to existing therapy, are sensitive to these agents,†said Pawel Osmulski, Ph.D., assistant professor of molecular medicine at the Health Science Center. He and Maria Gaczynska, Ph.D., associate professor of molecular medicine, co-authored a report in Molecular Pharmacology that provides a basis for this approach.
‘Highly beneficial’
Deregulation of the proteasome’s actions is noted in cancer or during aging and contributes to intracellular pathologies. “It is easy to envision that precise adjusting of the proteasome activities with therapeutic molecules would be highly beneficial in many human conditions,†Dr. Osmulski said.
Inhibition and activation