Brain tumours may need multiple drug treatment
Researchers have found that brain tumours often have more than one overactive cell-growth 'switch', explaining why treatment with a single drug designed to target one particular switch often fails.
The 'switches' are made of clusters of proteins, called receptor tyrosine kinase (RTK) molecules, and are often mutated and overactive in cancer cells. They are a major target for 'smart' cancer drugs - such as Gleevec and Tarceva - that each target a specific switch.
Located on the surfaces of cells, RTKs receive and transmit signals, including chemical growth factors that tell the cell to divide and grow.
Some RTKs have been implicated in glioblastoma multiforme (GBM), an aggressive brain tumour that is nearly always fatal. However, existing drugs are rarely effective.
Dr Ronald DePinho, director of the Centre for Applied Cancer Science at the Dana-Farber Cancer Institute, said: "Typically one elicits a positive initial response, but rarely durable cures.
"Overall, the record of receptor tyrosine kinase inhibitors in these brain tumours has been somewhat disappointing."
Researchers tested 20 glioblastoma cell cultures in order to measure the activity of different RTKs at any one time.
They found that, in 19 of the 20 cell lines, three or more RTKs were activated and emitting abnormal growth signals at the same time.
Similar results were observed in fresh tumour samples taken from newly-diagnosed patients.
Writing in the journal Science, the researchers said that the findings "provide a rational explanation for the feeble clinical responses" seen when a single targeted drug is given to patients.
They suggest that combination therapy is likely to achieve better results.
Dr DePinho commented: "This is a transformative finding that will motivate clinicians and our pharmaceutical colleagues to design clinical trials with regimens using several inhibitors," noting that three or more different drugs were required in the laboratory study to stop the abnormal cell growth signals.