The researchers validated the clusters in three additional data sets and also showed that even genes activated at similar levels in tumors in males and females can result in substantial sex-specific effects on survival.

“Additionally, we identified genetic pathways that correlated with the longest survival, and they were very different in males compared with females,” Rubin said. “For example, in males survival was all about regulating cell division, which suggests that drugs that block cell-cycle progression may be more effective in men. For females, survival was all about regulating invasiveness, which suggests that drugs targeting integrin signaling may be more effective in women. This tells us it might be better to separate males and females and examine their sex-specific genetic signatures. 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. In both males and females, there was a clear correlation.”


Among diseases in general, sex differences are often tied to hormones. For example, the female hormone estrogen contributes significantly to more women getting breast cancer than men. However, with glioblastoma diagnosis and survival, sex hormones did not directly contribute to female and male differences, Rubin said. “The sex-specific genetic activity in glioblastoma is not dependent on the acute actions of circulating sex hormones as differences are evident across all stages of life.”

“In a broader sense, I want our research to encourage people to think more about how diseases uniquely affect males and females, making it the norm and not the exception,” Rubin added. “I hope the research will inspire more specific approaches to treatments. 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.”

In addition to researchers at Washington University and the Mayo Clinic, scientists at the Cleveland Clinic, Case Western Reserve University and TGen, a genomics research institute, also contributed to the study.

This research was supported by National Institutes of Health (NIH) grants R01 CA174737, R01 NS060752, R01 CA164371, U54 CA210180, U54 CA143970, U54 CA193489, K08 NS081105, R01 NS094670 and U01 CA168397; the Children’s Discovery Institute of Washington University; Joshua’s Great Things; the James S. McDonnell Foundation; the Mayo Clinic; and the Ben & Catherine Ivy Foundation.

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