Study explores why glioblastoma affects sexes differently

A nationwide team of researchers that includes City of Hope’s Translational Genomics Research Institute (TGen) has identified molecular differences that explain why men die of glioblastoma, a type of brain cancer, at nearly twice the rate of women.
The study, published Jan. 2, 2019, in the journal Science Translational Medicine, could help tailor drug treatments that are specifically designed for men and women based on their tumors’ molecular subtypes.
“We have known for years that men contract and die from glioblastoma at a significantly higher rate than women,” said Michael Berens, Ph.D., TGen deputy director, head of the TGen Brain Cancer Research Laboratory and a contributing author of the study. “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.”
The research, led by Washington University School of Medicine in St. Louis, identified five distinct molecular signatures of glioblastoma in men, and five in women, that help explain the underlying disparities in patients’ response to treatments.
“It is our expectation that this study could have an immediate impact on the care of patients with glioblastoma, 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 Joshua B. Rubin, M.D., Ph.D., a Washington University professor and the study’s co-senior author.
Glioblastoma is an aggressive disease, with a median overall survival of only 15 months for newly diagnosed patients.

Studying adults with glioblastoma, researchers found that standard treatment is more effective in women than men. Researchers 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.
“The males did not respond as well, and we wanted to understand why, so we looked at the underlying genetics of patients’ tumors,” Rubin said.
“Josh Rubin’s results on sex differences in glioblastoma are very intriguing,” said Christine Brown, Ph.D., associate director of the T Cell Therapeutics Research Laboratory and the Heritage Provider Network Professor in Immunotherapy at City of Hope. “We will be retrospectively looking at our patient response in our CAR T cell trials to see if there are any sex-related differences.”