An essential mineral used to boost the immune system and block sunburns, zinc — in a different form — can also stabilize a protein that helps to prevent most cancers, according to a Wilmot Cancer Institute study.
But don’t rush to the local pharmacy and start taking zinc to prevent cancer, cautioned Darren Carpizo, M.D., Ph.D., the researcher who’s been investigating zinc’s role in cancer.
“You would never be able to get zinc levels high enough in your bloodstream by orally taking the common supplements,” explained Carpizo, a professor of Surgery at the University of Rochester Medical Center and chief of Surgical Oncology at Wilmot.
Zicam and other over-the-counter zinc formulations cannot cross cell membranes. A special transporter is needed for cells to absorb zinc, and this is where Carpizo’s research steps in: He and others are developing zinc-based drugs with a “chaperone” component, giving them the ability to deliver zinc directly to cancer cells.
In a recent study published in the science journal, eLife, Carpizo’s team showed how this powerful class of drugs, called zinc metallochaperones, could potentially treat more than 120,000 cancer patients annually in the U.S.
So far, the research has been confined to mice and cells in the laboratory. Carpizo founded a company, Z53 Therapeutics Inc., with the goal of commercializing the technology and transitioning the bench science to treatments.
Zinc’s potential as a cancer therapy stems from its specific role in preserving the proper function of the p53 gene, a protein located in the nucleus of all cells in the body. Under normal conditions, p53 suppresses tumors and keeps cancer at bay. But when mutations in p53 occur, it can no longer stop cancer cells from going rogue.
P53 is the most commonly mutated cancer gene and is believed to be a factor in nearly every type, most often breast, bladder, lung, ovarian, head and neck cancers, and in Li-Fraumeni syndrome, an inherited condition in which a person is at high risk for a specific group of cancers. Routine genetic testing or DNA sequencing of patients’ tumor samples can reveal the prominence of p53 mutations.
In 2012, Carpizo’s research team discovered that zinc metallochaperones could reactivate p53 and restore it as a cancer fighter. That prompted additional work, outlined in the latest paper, showing, first, the mechanisms that keep zinc from binding properly to p53 proteins; and then how to restore proper zinc binding to mutant p53 proteins.
Researchers also discovered that by raising zinc levels in cells, zinc reactivates a pathway that stabilizes an unexpectedly broad group of p53 mutations that lead to cancer. Further calculations showed that mutations in six of the 22 most common p53-related proteins are responsible for more than 120,000 cancer cases a year, Carpizo said.
Consumers might know that zinc has also been studied in connection with the coronavirus pandemic. Zinc may inhibit a protein involved in COVID-19 and it also has been investigated as a coronavirus treatment in combination with other medications. While those studies have had mixed results, Carpizo said, it’s conceivable that zinc may have a positive impact on infectious diseases, and on some neurological conditions.
Carpizo’s work on zinc began during a nearly 13-year career at Rutgers University. He left New Jersey to join the University of Rochester in February of 2020. His surgical oncology specialty is hepatobiliary and pancreatic cancer, and other research interests focus on why cancer cells go dormant and what awakens the cells and causes recurrence of disease.
The co-corresponding author of the zinc article is Stewart Loh, Ph.D., a professor of Biochemistry and Molecular Biology at SUNY Update Medical University in Syracuse. The National Institutes of Health and the Breast Cancer Research Foundation funded their research.