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Single cancer, multiple diseases


New findings about one of the most common forms of brain cancer in adults, known as glioblastoma multiforme, could have implications for developing targeted therapies to treat specific forms of the disorder. Above, histopathological image of cerebral glioblastoma. (Courtesy: Wikimedia Commons)

UNC-CHAPEL HILL—The most common form of malignant brain cancer in adults is not a single disease, but a set of diseases, each with a distinct underlying process, new research finds.

Scientists believe that the study provides a solid framework for investigation of future targeted therapies that may improve the near uniformly fatal prognosis of this devastating cancer known as glioblastoma multiforme (GBM).

“Previous work has established that gene expression profiling can be used to identify distinct subgroups of GBM,” says senior study author, D. Neil Hayes from the Division of Hematology/Oncology at the University of North Carolina at Chapel Hill. “However, the exact number and clinical significance of these was unclear.”

The research was published in the January issue of the journal Cancer Cell.

Hayes and colleagues at the UNC Lineberger Comprehensive Cancer Center expanded on previous GBM classification studies and used expression profiling techniques to comprehensively analyze hundreds of GBM patient samples. The group was able to reliably identify four distinct molecular subtypes of GBM tumors.

The researchers, part of the National Institutes of Health’s The Cancer Genome Atlas (TCGA) Research Network, then went on to perform unique integrative analyses across multiple platforms to look for defining characteristics associated with each subtype. Their findings were quite striking, implying that there are distinct types of GBM and that each one is associated with a specific molecular process.

“We discovered a bundle of events that unequivocally occur almost exclusively within a subtype,” explains Hayes.

The researchers also report that the nature of these events indicate that the underlying disease process for each subtype may involve distinct cells of origin at a specific stage of differentiation.

The scientists say this finding has potential clinical significance because determining the cells of origin of GBM is critical for establishing effective treatment regimens. Clearly, given this new information, it makes sense that some drug classes would be expected to work for some tumor subtypes and not other.

In support of this conclusion, Hayes’s group found that response to aggressive chemotherapy and radiation differed by subtype.

Taken together, the findings represent an important step towards more rational therapies for GBM.

“It appears that the simple classification into these four subtypes carries a rich set of associations for which there is no existing diagnostic test,” Hayes says.

“This comprehensive genomic and genetic-based classification of GBM should lay the groundwork from an improved molecular understanding of GBM pathway signaling that could ultimately result in personalized therapies for groups of patients with GBM.”

Researchers from the Broad Institute of MIT, Harvard, Washington University School of Medicine, the University of California, San Francisco, the Lawrence Berkeley National Laboratory, the Mayo Clinic, SRA International, and the Walter and Eliza Hall Institute in Victoria Australia, contributed to the study.

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