Lab studies show that combining drugs that target a variety of developmental cell signaling pathways may do a better job of killing deadly brain tumors than single drugs that target one pathway at a time, according to a new study by Johns Hopkins Kimmel Cancer Center researchers.  The combined therapy approach apparently reduces tumor resistance to chemotherapy, they say.

The new research, described in the Dec. 15 issue of the journal Clinical Cancer Research, found that simultaneously blocking the so-called Notch and Hedgehog pathways, both critical in cell development, did more to decrease growth of human glioblastoma cells and tumor cell clusters compared with drugs aimed at just the Notch pathway. Most standard clinical treatments for glioblastoma currently target just one pathway.

“Our study indicates it may be necessary to simultaneously target multiple development signaling pathways to prevent cancers from becoming resistant to therapy,” says Charles Eberhart, M.D., Ph.D., the study’s senior author and associate professor of pathology, ophthalmology and oncology. “A single agent is not likely to work for prolonged periods.”
Glioblastoma is one of the most aggressive brain tumors, killing nearly every patient within two years.  Even when the tumors initially seem to respond to medication, they generally develop resistance. This led researchers to speculate that tumors might compensate for therapy directed against one cancer cell development pathway by turning on a different one.