Genome Sequencing Uncovers Therapy For Rare Brain Tumor

Source: University of California, San Francisco

Summary: Researchers used tumor genome sequencing identified the first potential targeted drug to treat chordoid gliomas, a rare type of brain cancer.

Brain tumors are among the deadliest forms of cancer, due in large part to their sensitive location and the challenge of performing surgery to remove them. Chordoid gliomas, a rare type of brain cancer that develops within the third ventricle, a fluid-filled pocket that helps cushion the brain. Although these tumors are slow-growing, their proximity to the hypothalamus a critical brain region involved in hormone production makes chordoid gliomas difficult and potentially deadly to remove. A new research led by the researchers from the University of California, San Francisco used tumor genome sequencing identified the first potential targeted drug to treat chordoid gliomas. This new research provides much-needed targeted treatment options for patients whose tumors cannot be surgically removed. The study findings were published in the journal Nature Communications.

Brain cancer

A microscopic image of chordoid glioma. Credit: University of California, San Francisco

The research team sequenced the genomes of 13 chordoid glioma tumors and identified a single mutation in one gene, PRKCA, that was consistent across all 13 samples. PRKCA is part of a key growth pathway, called MAP kinase, that is turned off in normal brain cells. The mutation in PRKCA activates this MAP kinase pathway, causing the cells to divide dangerously and form a tumor. Because the MAP kinase pathway is so commonly implicated in cancer, drugs that target it are already available and approved by the FDA. The researchers tested trametinib, a drug used to treat melanoma, on brain cells with the PRKCA mutation. The drug effectively stopped tumor growth in cells carrying the mutation.

Asst. Prof. David Solomon said, “Precision medicine for cancer is based on identifying the DNA alterations that are behind the tumor. Then we can figure out what that DNA alteration does inside the cells to cause the tumors to form”, “Once we know that, then we can predict drugs to give to inhibit the activated pathways and stop the tumor growth.”

More Information: Benjamin Goode et al, “A recurrent kinase domain mutation in PRKCA defines chordoid glioma of the third ventricle”, Nature Communications (2018). DOI: 10.1038/s41467-018-02826-8

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