During treatment, radiation is directed at tumors with the goal of lethally damaging the dividing cancer cells. But some cancer cells survive, and nearby healthy cells can also be affected, leading to unwanted side effects.
“The goal is to identify new molecular targeting drugs that might increase the effectiveness of radiation and possibly diminish the amount of radiation needed,” said Dr. Paul Harari, senior author of the studies. “These two studies bring cutting-edge molecular drug growth inhibitors to the forefront, with the hope that several years down the road they can be used in the clinic in combination with radiation to benefit cancer patients.”
“Combining radiation with targeted therapies is not a new approach, but that is where treatment is heading,” said Dr. Shyhmin Huang, a lead author of the studies. What is unique in this work is that the researchers were looking at drugs that reduce the ability of cells to recover from radiation damage, hoping the double hit to cancer cells would prevent them from surviving. “These particular drugs can link beautifully with radiation treatment because they affect DNA damage and repair,” Harari said.
In one case, they looked at a drug that promotes the activity of the anti-growth protein p53, a molecule that normally signals severely damaged cells to stop growing but is blocked from working in many different cancer types. In a second paper, they focused on a drug that targets two crucial proteins of the EGFR family that are overactive in various poor-prognosis head and neck cancers.
In both cell-culture tests and mouse models, they found that administering the combination of either drug with radiation treatment was more effective at curbing cancer cell growth, through a variety of growth inhibition or even cell-death mechanisms, than either treatment alone. As lead author Lauryn Werner puts it, “radiation is putting on the gas, and the inhibitor drugs are removing the brakes. They synergize nicely.”
Both drugs are currently in phase I/II clinical trials to test their safety and early efficacy, and Harari expects that future trials could include combinations with radiation therapy.
Both articles were published in the September 2015 issue of the journal Molecular Cancer Therapeutics and chosen by the journal as featured articles.
University of Wisconsin School of Medicine and Public Health