February 28, 2019, New York—A Ludwig Cancer Research study finds that inhibiting the activity of a specific protein in the cells of glioblastoma (GBM) tumors boosts their sensitivity to radiation in a mouse model of the brain cancer. The findings, which suggest an approach to improving treatment of the most common and aggressive type of brain tumor in adults, were published online February 28 in Cancer Cell.
GBM is extremely difficult to treat and has a median survival rate of 15 to 16 months after diagnosis. Radiation and chemotherapy are the standard-of-care treatments, but GBM tumors quickly develop resistance to these therapies. In the current study, researchers led by Frank Furnari, a member of the Ludwig Institute for Cancer Research at the University of California, San Diego, identified a mechanism by which such resistance develops. It involves a protein named PTEN, which is ordinarily a tumor suppressor. The researchers found that phosphorylation of PTEN—the addition of a phosphate molecule to an amino acid of the protein, in this case tyrosine 240—promoted DNA repair in tumors, reversing the effects of therapeutic radiation.
When scientists blocked tyrosine 240 phosphorylation in mouse models of GBM using inhibitors of the fibroblast growth factor receptor, the cancer cells became sensitive to radiation, extending survival of the mice.
“These findings are novel and provide a foundation to move forward with a clinical trial and hopefully expand our findings to other cancer types that use this mechanism to evade therapy”, said Furnari, who is also a professor of pathology at the University of California, San Diego.
The UC San Diego release from which this summary is derived can be found here.
About Ludwig Cancer Research
Ludwig Cancer Research is an international collaborative network of acclaimed scientists that has pioneered cancer research and landmark discovery for more than 40 years. Ludwig combines basic science with the ability to translate its discoveries and conduct clinical trials to accelerate the development of new cancer diagnostics and therapies. Since 1971, Ludwig has invested $2.7 billion in life-changing science through the not-for-profit Ludwig Institute for Cancer Research and the six U.S.-based Ludwig Centers. To learn more, visit www.ludwigcancerresearch.org.
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