Brain Tumor Analysis Aids Therapy

A new study has shown that screening glioblastoma brain tumors for two gene variations can reliably predict which tumors will respond to a specific class of drugs. This finding was reported in the November 2005 issue of The New England Journal of Medicine.

In the study, researchers performed genetic analysis on tissue from recurrent malignant glioblastoma patients, of whom 26 responded either very well or very poorly to the drugs erlotinib (Tarceva) and gefitinib (Iressa). Both drugs are epidermal growth factor receptor (EGFR) kinase inhibitors. Both have been approved by the U.S. Food and Drug Administration (FDA) to treat advanced lung cancer that does not respond to other treatments.

Glioblastomas that produced both EGFRvlll, an EGFR variant, and a gene called PTEN were 51 times more likely to shrink when treated with EGFR inhibitors than tumors without this combination of proteins, the researchers found. Patients whose tumors expressed these proteins and also received an EGFR inhibitor went almost five times longer before their tumors progressed (243 days vs 50 days). However, EGFR and HER2/neu activity had no effect on how tumors responded.

The findings suggest that both EGFRvlll and PTEN proteins are important for tumors to be susceptible to EGFR inhibitors. The data further suggest that EGFRvlll may act to sensitize glioblastoma cells, while PTEN loss may act as a resistance factor. Adjusting treatment based on each tumor's genetic activity could significantly prolong life for a subset of patients and may allow some patients to be treated with the most effective therapy immediately, before the tumors can grow and develop new mutations.

"The survival with glioblastoma is usually a year on average,” said Paul Mischel, M.D., of the David Geffen School of Medicine at the University of California at Los Angeles (USA), who led the study.




Related Links:
UCLA