Drug combination helped kill deadly cancer in mice

Adding an experimental drug to chemotherapy helped wipe out brain cancer cells in mice, offering a promising new treatment approach for the deadly cancer, U.S. researchers said on Tuesday.

They said a drug called a gamma secretase or Notch inhibitor, combined with Merck & Co's chemotherapy Temodar or temozolomide, dramatically improved survival in mice with glioblastoma multiforme.

Glioblastoma is the most common and most aggressive form of brain cancer in people.

Glioblastomas are horrendous tumors, and new therapies are desperately needed, said Alonzo Ross of the University of Massachusetts Medical School, whose study appears in the journal Cancer Research.

We found that this double therapy of combining temozolomide with a Notch inhibitor was highly effective at treating tumor cells in culture and in mice, he added.

The finding is exciting because several drug companies including Eli Lilly and Co and Merck are developing gamma secretase inhibitor drugs that block or inhibit Notch, a cell signaling pathway.

Ross said adding the Notch inhibitor into the mix appeared to make the chemotherapy more potent, apparently permanently stopping the tumor cells from growing..

In half of the mice given the combination treatment, tumors disappeared. In the other half, they shrank.

Lilly last week halted a trial of its drug semagacestat, a notch inhibitor, in Alzheimer's patients because their symptoms got worse.

But Ross said that may not be an issue in brain cancer patients. They were trying to keep people on the drug for a long period of time whereas we are talking about a transient period, Ross said.

I don't think one has to be concerned about the side effects.

More testing is needed before the treatment combination can be tried in people.

The team still needs to test the combination in tumors that have been treated by radiation, which is the standard regimen for patients with glioblastoma tumors.

Ross said it is not clear what effect radiation may have.

It may enhance it. We just don't know yet, he said.

In addition to Eli Lilly, AVEO Pharmaceuticals is developing a Notch inhibitor drug.