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UA cancer team targets cancer’s iron ‘addiction’ for potential treatment

If typical body cells consume iron as part of a healthy diet, then cancer cells devour it like peak athletes pound down protein and pasta.

A new paper in the Journal of the American Chemical Society shows how researchers can take advantage of this iron “addiction” to target cancer cells.

“Iron is important in the biosynthesis of DNA for all cells; but, for cancer cells, that need becomes extreme,” said senior author Elisa Tomat of the University of Arizona Cancer Center. “And so, cancer cells have all sorts of programs to try and acquire more iron than normal cells, and they try to retain it, too.”

Tomat said cancer cells need so much iron partly to keep up with the need to repair and copy DNA while rapidly proliferating and spreading.

“Cancer cells just acquire more iron, they retain more iron — they just seem to have a different handling of iron compared to normal cells,” she said.

Iron-targeting compounds

With this in mind, the team made iron-targeting compounds that cause cell death in cancer cells but leave other ones alive.

"The compounds may also enter normal cells and become activated in normal cells,” said Tomat. “However, we have found — by comparative studies in normal cells and cancer cells — that the cancer cells are just more susceptible to the compounds.”

The team’s approach builds on a widely available lab test called an MTT assay, which drug companies and other labs use to assess the health of mammalian cells. Healthy cells will take in a tetrazolium ion and, following various steps, transform it into formazan, changing the culture from yellow to purple.

Tomat and her colleagues realized they could leverage that transformation to help them deliver an iron chelator — a compound or molecule that likes to bind to iron ions and wrap around them like a ring or claw, effectively neutralizing them.

Approach may someday fight ovarian cancers

Iron chelators play a number of important roles in medicine, biology and chemistry, including cancer treatments.

“So, that was where we started from, and then we made a little collection of compounds, trying to optimize the properties that we needed for the assay in terms of stability, in terms of iron-binding properties,” said Tomat. “And then we ultimately identified two compounds that really worked quite well.”

The team is now patenting the process and refining it to minimize necessary dosage. They hope to advance it from the proverbial test-tube stage to clinical tests in the coming years.

Tomat says she’s keen to find out the technique can treat one of the lab’s focus areas: ovarian cancers.

“This is a type of cancer that tends to present resistance to current chemotherapy,” she said. “And so we really want to see if we can exploit this iron approach for a type of cancer, for which, at the later stages, really, there's very little options for patients right now.”

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Nicholas Gerbis joined KJZZ’s Arizona Science Desk in 2016. A longtime science, health and technology journalist and editor, his extensive background in related nonprofit and science communications inform his reporting on Earth and space sciences, neuroscience and behavioral health, and bioscience/biotechnology.Apart from travel and three years in Delaware spent earning his master’s degree in physical geography (climatology), Gerbis has spent most of his life in Arizona. He also holds a master’s degree in journalism and mass communication from Arizona State University’s Cronkite School and a bachelor’s degree in geography (climatology/meteorology), also from ASU.Gerbis briefly “retired in reverse” and moved from Arizona to Wisconsin, where he taught science history and science-fiction film courses at University of Wisconsin-Eau Claire. He is glad to be back in the Valley and enjoys contributing to KJZZ’s Untold Arizona series.During the COVID-19 pandemic, Gerbis focused almost solely on coronavirus-related stories and analysis. In addition to reporting on the course of the disease and related research, he delved into deeper questions, such as the impact of shutdowns on science and medicine, the roots of vaccine reluctance and the policies that exacerbated the virus’s impact, particularly on vulnerable populations.