- Between 10% and 26% of people who have cancer develop brain metastases — where cancer from primary tumors in other parts of the body spreads to the brain.
- The 39th President of the United States Jimmy Carter received a diagnosis of brain metastases from melanoma in August 2015.
- Researchers from Tel Aviv University, Israel have now identified a specific protein that, when blocked, significantly reduces the development of brain metastases in a mouse model.
Between 10% and 26% of people with cancer develop brain metastases, which means that cancer from primary tumors forming in other parts of the body spreads to the brain.
In August 2015, the 39th United States President Jimmy Carter received a diagnosis of metastatic melanoma, where melanoma cancer cells had spread to the brain.
While doctors were able to treat President Carter’s brain metastases with immunotherapy, not all treatments work for every person, and the need still exists for further therapies for brain metastases.
Researchers may now be getting closer to another therapy thanks to the results of a study recently published by researchers from Tel Aviv University in Israel.
Scientists there have identified a specific protein that can drive the formation of brain metastases. They also found that inhibiting the protein significantly reduces the development of brain metastases in a mouse model.
The study recently appeared in the journal Nature Cancer.
What are brain metastases?
Sometimes cancer cells enter the bloodstream, which allows them to spread from a specific area of the body to the brain. When this happens, a person can develop new tumors in the brain called brain metastases.
Any type of cancer can cause brain metastases. The most common types of cancer that cause this condition are:
- breast cancer
- lung cancer
Brain metastases generally have a poor prognosis, with 8.1% 2-year and 2.4% 5-year survival rates.
Dr. Kim Margolin, a medical oncologist and medical director of the Saint John’s Cancer Institute Melanoma Program at Providence Saint John’s Health Center in Santa Monica, CA, not involved in the current study, explained for Medical News Today that people fighting brain metastases face a number of challenges.
She told us:
“Patients can have neurologic deficits that could be analogous to a stroke, where they develop an inability to use one side of the body or one limb, a visual deficit, or difficulty speaking. They can also develop specific symptoms related to the mass in the brain, including a headache [or] bleeding, which can spread the damage.”
The need for new therapies
According to Dr. Neta Erez, professor and vice dean of the Faculty of Medicine at Tel Aviv University and lead author of this study, brain metastases are one of the deadliest forms of cancer metastasis, with survival rates of less than 1 year in many cases.
“The incidence of brain metastases has been increasing in recent years as a result of improved treatments in extracranial disease, and therefore developing better therapeutic strategies for brain metastasis is an urgent need,” she told MNT.
Dr. Trevan Fischer, a surgical oncologist and assistant professor of surgical oncology for Saint John’s Cancer Institute at Providence Saint John’s Health Center in Santa Monica, CA, not involved in the study, agreed.
“A lot of the drugs that we have for cancer patients that may be effective outside the brain don’t get into the brain through the blood-brain barrier as well or at all,” he explained. “And so any cancer that has a high propensity to have brain metastasis, having targets that get into the brain to treat them are highly sought after.”
“And it’s harder to treat once it gets there,” Dr. Fischer added. “The brain is a confined space within the skull and treatments can cause swelling, which can cause side effects. You never want to have cancer go to the brain and when it does, there are limited options.”
LCN2 and brain metastases
In this study, Dr. Erez and her team identified the protein Lipocalin-2 (LCN2) as a key factor in causing neuroinflammation in the brain.
They also discovered high levels of LCN2 in the blood of people with brain metastases were linked to disease progression and survival rate.
Using mouse model studies of melanoma and breast cancer brain metastases, researchers found if they genetically inhibited LCN2, the development of brain metastases and neuroinflammation was reduced.
They found that LCN2 levels in the blood of mice with melanoma and breast cancer metastases were greatly increased compared to healthy mice. And an increase in blood LCN2 foreshadowed the detection of brain metastases by MRI.
“LCN2 is a secreted protein that functions in the innate immune system and was originally discovered due to its ability to bind iron molecules as part of the inflammatory process in fighting bacterial infection,” Dr. Erez detailed.
“We found a previously unknown mechanism mediated by LCN2, showing that it plays a central role in the interactions between immune cells recruited to the brain (granulocytes) and brain glial cells (astrocytes),” she added. “Secretion of LCN2 promoted inflammation, recruitment of bone marrow-derived cells to the brain, and the formation of brain metastases.”
“We are surprised and excited to find that LCN2 levels were also high in patients with brain metastasis and that its levels correlated with worse prognosis. These findings establish LCN2 as a new prognostic marker and a potential therapeutic target.”
– Dr. Neta Erez
How could this help people like President Carter?
Dr. Santosh Kesari, a neuro-oncologist and director of neuro-oncology at Providence Saint John’s Health Center chair of the Department of Translational Neurosciences and Neurotherapeutics at Saint John’s Cancer Institute in Santa Monica, CA, and regional medical director for the Research Clinical Institute of Providence Southern California, told MNT this study explains how President Carter’s brain metastases formed.
“Basically, the systemic immune system causes activation through LCN2, then inflammation in the brain itself through astrocytes,” he detailed. “This leads to more immune cells going into the brain, and then that leads to tumor cells having an environment to grow better. And that may explain why he got brain metastasis.”
Dr. Fischer said that, in President Carter’s case, he was treated with some immunotherapy medication, which has been around for the last 1 to 2 decades.
“And those medicines do reach the brain and can cross that blood-brain barrier,” he continued.
“With anything, if we can find a mechanism that has a target — so a medicine that we can develop to block that mechanism from happening — a lot of those medicines have less side effects if they’re more specific to a certain target. Part of treating a cancer patient is obviously you want to get rid of cancer however you can, but you want to do it in a way where the side effects are minimal. And some of these side effects are even long-term and life-lasting.”
– Dr. Trevan Fischer
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