Personalized Chemotherapy Likely To Improve Treatment of Brain Cancer

Cancer researchers have found that cells of the aggressive and often fatal brain tumor glioblastoma multiforme (GBM) express several different activated receptor tyrosine kinases (RTKs) enabling them to survive treatment with a single chemotherapeutic agent.

Investigators at the Dana-Farber Cancer Institute (Boston, MA, USA) sought to explain why drugs that inhibit receptor tyrosine kinases (RTKs) and the downstream phosphatidylinositol 3-kinase (PI3K) signaling pathway were mostly ineffective in treating GBM and other solid tumors. "Typically one elicits a positive initial response, but rarely durable cures,” explained senior author Dr. Rondal DePinho, a professor of medicine at the Dana-Farber Cancer Institute. "Overall, the record of receptor tyrosine kinases inhibitors in these brain tumors has been somewhat disappointing.”

In their study the investigators used an antibody array technique that measured the activation of 45 different RTKs at one time. They tested 20 glioblastoma cell lines as well as fresh tumor cells taken from recently diagnosed cancer patients. Results published in the September 13, 2007, online edition of Science revealed that in 19 of the 20 cell lines, three or more RTKs were activated at the same time, sending abnormal growth signals in triplicate to the cells. The same multiple-RTK activity was also found in samples from newly diagnosed cancer patients. Treatment of the cancer cells with the kinase inhibitor imatinib had little effect on RTK activity. However, when imatinib was given in combination with two other kinase inhibitors, erlotinib and SU11274, traffic in the PI3K signaling pathway was eliminated, and the cancer cells died.

The investigators anticipate being able to design a personalized chemotherapeutic approach for individual patients after establishing a profile comprising the number and type of aberrant RTKs expressed by that patient's tumor cells.


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Dana-Farber Cancer Institute