The gene, called Notch2, whose pathway is known to be an important factor in regulating brain stem-cell growth and survival, has been studied in fruit flies for almost a century. The research team at the Johns Hopkins Pathology Department and Kimmel Cancer Center found that a protein made by the Notch2 gene promotes cancer cell growth by 27 percent in a childhood brain tumor, called medulloblastoma. Their studies, reported in the November 1 issue of Cancer Research, also revealed that children with high Notch2 gene activity fared worse in the course of their disease than those with less activity in Notch2.
The researchers report that a drug first developed for Alzheimer's disease called DFK-167, which blocks activation of all Notch proteins, reduces growth of cancerous cells in culture by 80 percent, although unwanted side effects and dosing problems may make it a poor choice for treating human brain cancer. But the investigators are testing more potent drugs of the same class and developing new ones that block only the Notch2 pathway.
No clinical trials with any drug have yet been planned, the researchers emphasize.
Scientists say that gene amplification - a process in which cells make too many copies of a gene -- is one of the most reliable indicators of a gene's importance to cancer development. The Johns Hopkins team found Notch2 amplified in six of 40 (15 percent) medulloblastomas and other similar brain tumors.
"Just like genetic mutations, amplifications are long-lasting DNA mistakes, as opposed to transient changes in the production of proteins and other gene products," says Charles Eberhart, M.D., Ph.D., assistant professor of pathology at Johns Hopkins. "Finding amplification of Notch2 is a smokin
Contact: Vanessa Wasta
Johns Hopkins Medical Institutions