BOSTON--Researchers at Dana-Farber Cancer Institute have shown that several, rather than just one, cell-growth switches are simultaneously overactive in many brain tumors and other solid tumors, explaining why treatment with just a single "targeted" switch-blocking drug often yields disappointing results.
The laboratory finding argues for quickly moving to clinical trials that combine three or more such targeted drugs for such cancers to shut down all the malfunctioning growth switches, according to the team led by Ronald DePinho, MD, director of the Center for Applied Cancer Science at the Dana-Farber. Their report is being posted online on Sept. 13 by the journal Science and will appear in a forthcoming print issue.
The switches are formed by molecules called receptor tyrosine kinases (RTKs) that often are mutated and hyperactive in cancer cells. Since a number of kinase-blocking drugs are already available -- Gleevec and Tarceva are two of the best-known -- the researchers said clinical trials of combinations of the compounds should be planned quickly.
"This is a transformative finding that will motivate clinicians and our pharmaceutical colleagues to design clinical trials with regimens using several inhibitors," said DePinho. He noted that in the laboratory study using cancer cell lines and fresh specimens of brain tumors, three or more kinase inhibitors were needed to quell the abnormal cell-growth signals.
The study focused on glioblastoma multiforme (GBM), an aggressive brain tumor that is nearly always fatal. The scientists also found similar patterns of multiply activated RTKs in other common cancers of the pancreas and lung.
Jayne Stommel, PhD, lead author of the report and a post-doctoral fellow in the DePinho lab, undertook a survey of molecular RTK "signaling pathways" in GBM cells to find the sources of abnormal growth.
RTKs are located on the surface of both normal and cancerous cells and rec
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Dana-Farber Cancer Institute