Predicting the Response of Glioblastoma to EGFR Inhibitors
Patients with glioblastoma multiforme are more likely to respond to treatment with erlotinib or gefitinib if their glioblastoma cells have a specific variant of the epidermal growth factor receptor (EGFR) as well as the PTEN tumor suppressor protein, according to a study published in the New England Journal of Medicine.
Approximately 20,000 people are diagnosed with primary brain cancer in the U.S. each year. Primary brain cancer is cancer that originates in the brain, as opposed to cancer that has spread to the brain from elsewhere in the body.
Glioblastoma is one of the most common and fatal types of primary brain cancer. When glioblastoma is present, glial cells become malignant and grow rampantly. Glial cells are the most abundant cells present in the nervous system. They provide many supportive functions that facilitate the majority of processes conducted by neurons (cells that transmit impulses between the brain, spinal column, and nerves).
Standard treatment options for glioblastoma consist of surgical removal of the cancer when possible, radiation therapy, and/or chemotherapy. However, even with the most aggressive treatment available, most patients will only survive less than one year after diagnosis. Due to this poor prognosis, researchers are attempting to develop more effective treatment strategies to improve survival of glioblastoma patients.
Several promising cancer therapies target the epidermal growth factor receptor (EGFR) pathway, which is involved in the replication of cells. Although EGFR is frequently amplified in glioblastoma, only 10%-20% of glioblastoma patients respond to drugs that inhibit EGFR, such as gefitinib and erlotinib. Researchers are therefore trying to identify characteristics of glioblastoma cells that will help predict which patients are most likely to benefit from EGFR inhibitors.
In order to assess whether the presence of a specific variant of EGFR (EGFRvIII) or the presence of the PTEN tumor suppressor protein influence response to treatment with gefitinib or erlotinib, researchers evaluated 49 patients with recurrent glioblastoma. Thirty-seven of the patients were treated with gefitinib and 12 were treated with erlotinib. Nine of the total 49 patients had at least a 25% reduction in tumor size following treatment. Tumor tissue was available for 26 patients, seven of whom had responded to treatment and 19 of whom had disease that progressed during treatment.
The researchers found that patients who had evidence of both EGFRvIII and PTEN in glioblastoma cells were much more likely to respond to treatment with erlotinib or gefitinib than patients who had neither of these characteristics. They conclude that EGFRvIII and PTEN are involved in the response of glioblastoma multiforme to EGRF kinase inhibitors such as erlotinib and gefitinib and may be useful in predicting treatment response.
Reference: Mellinghoff IK, Wang MY, Vivanco I et al. Molecular Determinants of the Response of Glioblastomas to EGFR Kinase Inhibitors. NewEnglandJournal of Medicine. 2005;353:2012-24.