MAP Kinase Activation Causes Deadly Brain Tumor

A gene mutation linked to chordoid gliomas may result in targeted treatment options.

Due to brain sensitivity and the risks associated with performing surgery, brain tumors remain one of the deadliest forms of cancer. New findings could lead to targeted treatment options for patients with brain tumors that cannot be surgically removed.

Chordoid gliomas, a rare type of brain cancer, are notoriously dangerous to remove. The discovery of a gene that may play a role in the development of chordoid gliomas may lead to an effective therapy, according to a study published by Nature Communications.

Chordoid gliomas grow in the third ventricle of the brain, which is filled with fluid that provides cushioning to the brain. The cancer progresses slowly, but its proximity to the hypothalamus makes it almost impossible to remove, leaving patients with few effective treatment options, according to the study.

In the study, the authors examined the genome sequences of 13 chordoid gliomas and discovered the mutation of a single gene across every tumor.

The gene, PRKCA, plays a key role in MAP kinase, a growth pathway that is dormant in healthy brain cells. Mutations of PRKCA activate the MAP pathway, causing the cells to divide rapidly and form a cancerous tumor.

Although PRKCA has not been identified in any other type of cancer, most human tumors develop from a mutation that effects the MAP kinase in some way, according to the authors.

Because the MAP pathway is known to be involved with cancer development, drugs that target it have already been FDA-approved and launched.

The researchers then tested trametinib—an MEK inhibitor approved for melanoma—on brain cells with a PRKCA mutation. Researchers discovered that trametinib effectively stopped the development of tumors from the mutation in brain cells.

The authors noted that this finding is groundbreaking and may open the door to new therapies for chordoid gliomas.

“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,” said lead researcher David Solomon, MD, PhD. “Once we know that, then we can predict drugs to give to inhibit the activated pathways and stop the tumor growth.”

The authors are currently working to design a nationwide clinical trial for patients with chordoid gliomas.