Researchers Potentially Uncover Technique to Delay Spread of Melanoma to the Brain

In an encouraging new study, researchers from Tel Aviv University have potentially found a way to delay the metastasization of melanoma to the brain, which occurs in 90 percent of melanoma patients at advanced stages, according to lead author Ronit Satchi-Fainaro, PhD, head of Cancer Research and Nanomedicine Laboratory at Tel Aviv University. Ideally, this new technique will lead to better prognoses for melanoma patients.

The blood-brain barrier, which prevents harmful substances from entering the brain, seems to consistently fail when it comes to melanoma metastasizing. Satchi-Fainaro and her team were able to track down the responsible mechanism: astrocyte “recruitment.” Astrocytes, which are cells located in the brain and spinal cord, are responsible for maintaining brain homeostasis. They are the first responders in the event of a stroke or other trauma, Satchi-Fainaro explains. In the case of melanoma metastasis, the astrocytes secrete a protein called monocyte chemoattractant protein-1 (MCP-1) that causes inflammation, thus making the blood-brain barrier more permeable. Then, the cancer cells express receptors CCR2 and CCR4, essentially promoting cancerous growth and spreading to the brain.

To test this, the researchers blocked the expression of MCP-1 by means of an antibody and a synthetic molecule designed for this purpose. Then, they used CRISPR technology to remove the two genes that express the CCR2 and CCR4 receptors in the cancerous cells. By stifling the protein and removing the receptors, the interplay between astrocytes and malignant cells was inhibited, delaying the spread of malignant cells to the brain.

“These treatments succeeded in delaying the penetration of the cancer cells into the brain and their subsequent spread throughout the brain,” says Satchi-Fainaro concerning the testing they performed on mice. “I believe that the treatment is suitable for the clinic as a preventative measure.” In their research, the team achieved a 60 to 80 percent delay, which varied based on when the intervention took place in the treatment process. They achieved the best results after surgery to remove the primary melanoma, successfully preventing the metastases from entering the brain.

This research was conducted in collaboration with the NIH, Johns Hopkins University, and the University of London.

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