Healthcare providers should consider treating men and women with glioblastoma (GBM) in different ways, according to a study published in Science Translational Medicine. The authors measured tumor growth velocity in MRI scans to reach this conclusion.
“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 Joshua B. Rubin, MD, PhD, a professor of pediatrics and neuroscience of the Washington University School of Medicine in St. Louis (WUSTL), in a prepared statement. “The biology of sex differences and its applications in medicine are highly relevant but almost always ignored aspects of personalized treatments.”
The team viewed MRI scans and calculated the speed of tumor growth every two months in 63 glioblastoma patients. While 40 patients were male, 23 were female. All patients received traditional standard chemotherapy and radiation following surgery.
While initial tumor growth speed was comparable in both genders, only the females exhibited “a steady and significant decline in tumor growth” after treatment with temozolomide, a conventional chemotherapy drug.
“Basically, you can look at tumor growth velocity while patients are undergoing treatment and derive a value for how fast their tumors are growing,” Rubin noted in the same statement. “This gives you an opportunity to think more deeply about whether the drug you’re giving a patient is actually helping.”
Rubin et al. investigated further to better understand why the male patients did not respond well to the medication. They applied algorithms to determine male and female-specific gene patterns and further examined the gender-specific genes to establish molecular subtypes that matched with the survival for males and females.
“We observed tremendous genetic sex differences in the tumors of glioblastoma patients that correlated with survival,” Jingqin Luo, PhD, the study's lead author, said in the same statement. “All evidence supports the need to define these distinctions and incorporate the sex differences into glioblastoma biology research and treatment.”
The team found found the tumors in glioblastoma patients are grouped into 10 subtypes—five for male and five for female, which are known by gene activity and survival. These subtypes were validated three times as confirmation. Rubin noted his team identified genetic pathways that were associated with the longest survival—which were very different in males compared to females. They found that drugs that obstruct cell-cycle progression are more apt for males and drugs that target integrin signaling are more apt for females.
“We tested this hypothesis by doing a series of in vitro drug screens in which we took four relatively common chemo drugs and looked at how the expression of these genes correlated with response to those drugs,” Rubin said. “In both males and females, there was a clear correlation.”
Rubin hopes people will continue to examine how diseases uniquely affect males and females.
“I hope the research will inspire more specific approaches to treatments,” he said. “It may be that we shouldn’t be using the same criteria when treating diseases in males and females, and as a next step we should definitely develop and evaluate sex-specific treatment regimens for glioblastoma.”