Glioblastoma map points to new protein targets and immuno-oncology approaches

There has been little progress in the search for cures for the aggressive brain cancer glioblastoma, largely because of a lack of understanding of how the tumor cells interact with the immune system and other cells and tissues in the body. A new glioblastoma map was designed to fill in some of those knowledge gaps.

A study of 99 tumors resulted in a map of genes, proteins, cells and signaling pathways that are active in glioblastoma. Scientists at the Washington University School of Medicine, Pacific Northwest National Laboratory, Case Western Reserve University and the National Cancer Institute (NCI) contributed to the map, which was published in the journal Cancer Cell.

The map revealed potential new drug targets for treating glioblastoma, including the proteins PTPN11 and PLCG1. The researchers discovered that the two proteins act as “signaling hubs” that drive tumor growth in some patients, according to a statement.

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The researchers also scrutinized the quantity and types of immune cells present in glioblastoma tumors. By combining proteomic and genomic analysis, they identified four different immune subtypes of the disease. "This may open the door for effective responses to immune therapies," said Henry Rodriguez, director of the Office of Cancer Clinical Proteomics Research at the NCI, in the statement.

Immunotherapy has so far not made inroads in the treatment of glioblastoma, though there are several research efforts underway to try to change that. Last October, a Swiss team published a study showing that antibodies combined with immune-stimulating cytokines slowed the growth of glioblastoma tumors in mice.

Ziopharm has been testing IL-12 along with a PD-1 inhibitor in glioblastoma with promising results. Last year, the company reported results from a small clinical trial in which patients who were given the combination, along with a steroid, lived a median of 16.2 months, a result CEO Laurence Cooper, M.D., Ph.D., called “very, very encouraging.”

The next step for the researchers who developed the new glioblastoma map is to search for drugs to test in patients based on where their tumors reside on that map. “This multifaceted analysis provides an unprecedented level of detail,” said co-senior author Tao Liu, Ph.D., of Pacific Northwest National Laboratory, “which is starting to connect the missing dots in glioblastoma."