Can a metabolic flaw in cancer cells be exploited to improve treatments for head and neck cancers?
That's the question that Douglas Spitz, PhD, professor of radiation oncology in the University of Iowa Roy J. and Lucille A. Carver College of Medicine, and his colleagues will seek an answer with a five-year, $1.5 million grant from the National Cancer Institute, part of the National Institutes of Health.
Previously, Spitz and his team have shown that tumor cells are more sensitive than normal cells to oxidative stress caused by glucose deprivation. The researchers are now investigating ways to exploit this metabolic difference to improve cancer therapies.
With the new grant, the team will test whether combining therapies that increase oxidative stress with compounds that impair the cells' ability to handle oxidative stress will deal cancer cells a lethal "double whammy."
The research follows findings from Spitz's lab suggesting that cancer cells need more glucose than normal cells to overcome a flaw in the cell's oxidative metabolic processes. The flaw leads to excess production of toxic substances that cause oxidative stress. The research suggests that cancer cells require extra glucose to help remove these toxic substances.
The new study will investigate whether blocking the cancer cell's "detoxification" mechanisms makes the cells more susceptible to standard therapies, which further boost oxidative stress. These standard therapies include radiation and cisplatin.
"If our experiments show that these hypotheses are correct, they could provide the first mechanism-based, biochemical rationale for using differences in glucose and oxidative metabolism to develop combined-modality therapies to treat head and neck cancer," said Spitz, who also is director of the Free Radical and Radiation Biology Program at the UI.
The researchers also will determine whether tumors with the highest levels of glucose uptake are the most susceptible to the combined treatment. This information could eventually help physicians diagnose which tumors might be most treatable using approaches that target defective oxidative metabolism.
Spitz's co-investigators include:
Spitz, Hichwa and Graham all are members of Holden Comprehensive Cancer Center at the UI.
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For more information:
Douglas Spitz, PhD
Spitz's lab
Free Radical and Radiation Biology Program
Holden Comprehensive Cancer Center
UI Roy J. and Lucille A. Carver College of Medicine
National Cancer Institute
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