If we can determine the mechanisms of resistance to a drug, then we can opt for different therapy or, eventually, alter that mechanism of resistance. While growing human GBM tumors on mouse models, the researchers treated the tumors with procarbazine, a drug commonly prescribed alone or in combination with other drugs in therapy for the brain cancer. Though procarbazine is a frontline drug treatment, most patients ultimately develop resistance to it and it ceases to check tumor growth. The tumors growing on mice developed resistance to the drug after nine serial treatments, giving the researchers a way to study the resistance mechanism. In the normal sequence of cell replication, the attached compounds alert the mismatch repair mechanism in the cell that a mutation has occurred, according to Friedman.
All cells go through changes, or mutations, day to day.
When mismatch repair is inactivated, you predispose cells to a high mutation rate. If the findings from the xenograft, or animal-grown, tumors bear out, clinical application could begin in trials in the next year, Friedman said. Other researchers on the project are Stewart Johnson, Qing Dong, Clifford Schold, Ahmed Rasheed, Dr. Sandra Bigner, Francis Ail-Osman, Eileen Dolan, Dr. Michael Colvin, Peter Houghton, Glen Germain, James Drummond, Stephen Keir, Susan Marcelli and Dr. Darell Bigner.