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Cleveland Clinic, CWRU receive $10.4 million to study differences in glioblastoma between sexes - Crain's Cleveland Business

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Researchers from Case Western Reserve University School of Medicine and Cleveland Clinic's Lerner Research Institute are leading a team that has secured $10.4 million to explore at the molecular level the differences in glioblastoma between males and females, according to a news release.

The five-year grant from the National Institutes of Health/National Cancer Institute will support the researchers as they delve into the genetics, epigenetics (the study of changes in gene function that are heritable and not attributed to DNA sequence alterations) and the cell biology of glioblastoma, which is the most common and deadliest brain tumor in adults, according to the release. The goal is to gain better understanding of physiologic processes, which could lead to more personalized therapies.

Despite available treatments, the median survival time for glioblastomas is 12 to 14 months, with only about 5% of patients surviving more than five years, according to the release.

Previously, the researchers published work that showed significant differences between the sexes in glioblastoma incidence, survival and key molecular pathways. Glioblastoma is 60% higher in males than females, who also have a significant survival advantage over males with a median improved survival rate of up to 10 months, according to the release. Though the sex differences are understood, they're not yet considered when in the treatment of glioblastoma.

"Sex differences are inherent drivers of glioblastoma incidence and survival, and we are taking a multidimensional approach to uncover a better understanding of this differentiation," said Justin Lathia, a co-principal investigator on the multidisciplinary project, in a provided statement. "We are incorporating data from tumor cells and their surrounding micro-environment, as well as genetic programs responsible for tumor growth, and underlying epigenetic differences that may be responsible for sex differences. We aim to gain a better understanding of how these variables interrelate to better understand disease mechanism, which in turn defines better diagnostics and more personalized therapies for patients."

Lathia is vice chair of the Department of Cardiovascular and Metabolic Sciences and co-director of the Brain Tumor Research & Therapeutic Development Center of Excellence at Lerner Research Institute, as well as co-leader of the Molecular Oncology Program at the Case Comprehensive Cancer Center.

Jill Barnholtz-Sloan, of CWRU School of Medicine, is the other co-principal investigator and with Lathia will lead the team, which also includes: Dr. Joshua Rubin of Washington University School of Medicine in St. Louis, James Connor of Penn State College of Medicine, and Michael Berens of Translational Genomics Research Institute (TGen).

The collaborative team will work on three related research projects that delve into the basic biology and cellular mechanisms that drive sex differences in glioblastoma formation and progression, according to the release.

"We have the molecular profiling technology and the computing and analytical strength to lead in this effort to better understand the role of sex differences in cancer, particularly for glioblastoma," said Barnholtz-Sloan, the Sally S. Morley Designated Professor in Brain Tumor Research and associate director of Data Sciences at the Case Comprehensive Cancer Center, CWRU School of Medicine, in a provided statement. "This next phase of research relies on vast, varied and complex datasets — in animals and humans — and promises to be a game-changer in how we understand the role of sex in tumor formation and disease outcomes. This comprehensive approach has applications to all forms of cancer, as well as other diseases."

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Cleveland Clinic, CWRU receive $10.4 million to study differences in glioblastoma between sexes - Crain's Cleveland Business
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