In advanced stages of skin cancer, patients develop brain metastases about 90% of the time. Though this is one of the most common complications of late-stage melanoma, it is also one of the most difficult to treat.
Brian metastases are difficult to treat for a multitude of reasons. They are typically very aggressive and patients may not experience symptoms until there are multiple lesions in the brain. Treatment options may also damage surrounding brain tissue. Without therapeutic intervention, metastatic lesions lead to a median survival of fewer than seven months.
New research from scientists at Tel Aviv University is shedding light on why brain metastases are such a common complication in late-stage melanoma. The researchers found that in melanoma patients with brain metastases, the cancer cells recruit astrocytes, star-shaped cells found in the spinal cord and brain which are responsible for maintaining stable conditions in the brain.
Professor Satchi-Fainaro, study co-author, says that "astrocytes are the first to come to correct the situation in the event of a stroke or trauma... it is with them that the cancer cells interact, exchanging molecules and corrupting them.”
As the cancer cells recruit astrocytes, they create local inflammation in areas that increase permeability through the blood-brain barrier. At this point, the astrocytes begin to secrete a protein called MCP-1 that promotes inflammation.
Using this information, the team of researchers used an antibody to block the MCP-1 protein in the hopes of inhibiting the expression of the protein and its receptors. They also used CRISPR technology to remove two genes from the cancer cells that express the corresponding receptors.
Both of these methods resulted in a delay in the spread of metastases. "These treatments succeeded in delaying the penetration of the cancer cells into the brain and their subsequent spread throughout the brain,” says Professor Satchi-Fainaro.
“It's important to note that melanoma metastases in the brain are very aggressive with a poor prognosis of 15 months following surgery, radiation and chemotherapy. We reached a 60% to 80% delay, depending on the stage of the intervention.”
The researchers believe that these treatments are considered safe and can be used to treat melanoma. The antibody that was used in the study is already used as a treatment for other conditions, which suggests that it is safe for clinical use.
Sources: AIM at Melanoma Foundation, JCI Insight
