Breakthrough in disease that felled Arizona ‘maverick’ John McCain

A team of researchers has announced a breakthrough in glioblastoma, the lethal form of brain cancer that United States Senator John McCain of Arizona battled last year.

A nationwide team, including researchers from the Phoenix nonprofit TGen, has identified molecular differences that reveal why men die of glioblastoma brain cancer at much higher rates than women. This discovery could help tailor drug treatments that are specifically designed for men and women.

“We have known for years that men contract and die from glioblastoma at a significantly higher rate than women,” said Dr. Michael Berens, who heads TGen’s Brain Cancer Research Laboratory, and is contributing author of the study that was published in this month’s issue of Science Translational Medicine. “We now have a much clearer understanding of this phenomenon, and this study should help us in the future to improve survival for all glioblastoma patients.”

McCain, a longtime U.S. Senator and former Vietnam prisoner of war, fought his final battle for 12 long months before his family announced on Aug. 24 that he would stop treatment.

He succumbed the next day. His death was exactly nine years after the death of Senator Edward “Ted” Kennedy, another victim of glioblastoma.

Glioblastoma is very aggressive. Newly diagnosed patients have a median overall survival of 15 months. One of the major difficulties in treating it is its intrusive penetration into adjoining tissues that prevents the complete surgical removal of the tumors from the brain, even with follow-up radiation and chemotherapy. As a result, nearly all glioblastomas recur.

Researchers now have identified five distinct molecular signatures of glioblastoma in men and five in women that help explain the underlying disparities in response to treatments.

Studying adults with glioblastoma, researchers found that standard treatment is more effective for women. They reviewed patient MRI scans and survival data from a cancer research database. They then calculated tumor growth velocity every two months for the duration of therapy in 63 glioblastoma patients — 40 males and 23 females — who received standard chemo-radiation treatment following surgery.

While initial tumor growth velocities were similar between women and men, only females showed a steady and significant decline in tumor growth after treatment with temozolomide, the most common chemotherapy drug used to treat glioblastoma.

Researchers tapped The Cancer Genome Atlas (TCGA) — a project launched in 2005 to pursue the genetic basis of cancer and funded by the National Cancer Institute and National Human Genome Research Institute, both at the National Institute of Health (NIH).

“It is our expectation that this study could have an immediate impact on the care of patients with glioblastoma and further research, as the findings indicate we should be stratifying male and female glioblastoma into risk groups and evaluating the effectiveness of treatment in a sex-specific manner,” said Dr. Joshua Rubin, a Washington University professor of pediatrics and of neuroscience and co-senior author of the study. “The biology of sex differences and its applications in medicine is a highly relevant but almost always ignored aspect of personalized treatments.”

In addition to researchers at TGen and Washington University, scientists and physicians at Mayo Clinic, Cleveland Clinic and Case Western Reserve University also contributed to this research.

TGen, which stands for Translational Genomics Research Institute, is an affiliate of City of Hope, a private, not-for-profit clinical research center and a founding member of the National Comprehensive Cancer Network (NCCN), a non-profit alliance of 21 U.S. cancer centers.