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  • Posted Wednesday January 2, 2019

TGen joins in study that shows ignoring sex differences in personalized treatments can be deadly

Study led by Washington University explains why more men than women succumb to glioblastoma

PHOENIX, Ariz. — Jan. 2, 2019 — A nationwide team of researchers that includes the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, has identified molecular differences that explain why men die of glioblastoma brain cancer at nearly twice the rate of women.

The study, published today in the prestigious scientific 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 Dr. Michael Berens, 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 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 B. Rubin, a Washington University professor of pediatrics and of neuroscience, and the study’s co-senior author. “The biology of sex differences and its applications in medicine is a highly relevant but almost always ignored aspect of personalized treatments.”

Glioblastoma is an aggressive disease, with a median overall survival of only 15 months for newly diagnosed patients. One of the major difficulties in treating glioblastoma is its intrusive penetration into adjoining tissues, which 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. Patients whose brain cancer returns are often encouraged to enter experimental clinical trials. However, even on clinical trials, further progression of the disease is seen, on average, within 4 months.

Studying adults with glioblastoma, researchers found that standard treatment for glioblastoma 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,” said Dr. Rubin, the co-leader of the Solid Tumor Therapeutics Program at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine.

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 Institutes of Health (NIH). Researchers applied sophisticated statistical algorithms to distinguish male- or female-specific gene expression patterns. The team then focused on the sex-specific gene expression to identify molecular subtypes that corresponded to differences in survival for men and for women.

Specifically, the researchers showed that the tumors of patients with glioblastoma cluster into 10 distinct subtypes — five for tumors in males, and five for tumors in females. The clusters are distinguished by gene activity and length of survival.

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.

This study — Clinically Important Sex differences in GBM biology revealed by analysis of male and female imaging, transcriptome and survival data — 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; and The Ben & Catherine Ivy Foundation.

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About TGen, an affiliate of City of Hope
Translational Genomics Research Institute (TGen) is a Phoenix, Arizona-based non-profit organization dedicated to conducting groundbreaking research with life changing results. TGen is affiliated with City of Hope, a world-renowned independent research and cancer and diabetes treatment center: This precision medicine affiliation enables both institutes to complement each other in research and patient care, with City of Hope providing a significant clinical setting to advance scientific discoveries made by TGen. TGen is focused on helping patients with neurological disorders, cancer, diabetes, and infectious diseases, through cutting edge translational research (the process of rapidly moving research towards patient benefit).  TGen physicians and scientists work to unravel the genetic components of both common and rare complex diseases in adults and children. Working with collaborators in the scientific and medical communities literally worldwide, TGen makes a substantial contribution to help our patients through efficiency and effectiveness of the translational process. For more information, visit: Follow TGen on FacebookLinkedIn and Twitter @TGen.

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Galen Perry
Vice President, TGen Marketing and Communications
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Steve Yozwiak
TGen Senior Science Writer
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