Israeli discovery may help fight risk of skin cancer triggering brain tumors

Israeli scientists believe they’ve made progress in fighting the common phenomenon of skin cancer triggering secondary cancer in the brain.

Researchers at Tel Aviv University believe they have identified a key mechanism that leads skin cancer to prompt brain cancer — though they stress that it has so far only been tested on human tissue in lab conditions so far.

The scientists built a lab model that simulates the human body, consisting of cancerous tissue from skin, blood, and brain tissue, all arranged in the lab in a manner that causes them to mimic their interaction in the body. They then managed to reduce the incidence of secondary cancer by 60%, by using existing drugs.

“Some 90% of melanoma patients — skin cancer patients — in an advanced stage will develop brain metastases, meaning secondary malignant growths,” said lead researcher Prof. Ronit Satchi-Fainaro.

“Our treatments succeeded in delaying the penetration of the cancer cells into the brain and their subsequent spread throughout the brain.”

Her research, newly peer-reviewed and published in the journal JCI Insight, suggests that skin cancer cells cause normal cells to go rogue by expressing two proteins, called CCR2 and CCR4.

Her hypothesis is that they prompt brain cells called astrocytes, which normally maintain stable conditions in the brain, to stop fulfilling their usual role and cause instability instead.

Illustrative image of a dermatologist checking a mole on a patient for signs of melanoma (AlexRaths; iStock by Getty Images)

She told The Times of Israel: “The melanoma cells leave the primary tumor on the skin, enter into the blood, and while circulating in the blood, they release proteins that communicate with astrocytes in the brain. Based on instructions from these proteins, the astrocytes become activated and release other proteins that basically call melanoma cells to come to the brain.

“So instead of fighting the cancer cells as they should, astrocytes are helping cancer cells to migrate to the brain, invade the brain tissue and grow.”

Her team, which included Prof. Adi Barzel, Dr. Asaf Madi, Prof. Iris Barshack, Prof. Eran Perlson, and Prof. Inna Slutsky, tried several approaches to stop the harmful proteins from reaching the brain. It achieved particular success with an antibody and, separately, with a synthetic drug comprised of a small molecule — both of which have already been developed as treatments for other conditions.

Left to right, Tel Aviv University researchers Sabina Pozzi and Prof. Ronit Satchi-Fainaro. (Courtesy of Tel Aviv University)

“Both the antibody and the small molecule we used — which are primarily intended to treat sclerosis, diabetes, liver fibrosis, and cardiovascular diseases — have already been tested on humans as part of clinical trials,” Satchi-Fainaro explained. “Therefore, these treatments are considered safe, and we can try to repurpose them for melanoma.

“They worked by stopping the proteins which cause the interactions between the melanoma cells and the astrocytes in the brain, and they return astrocytes to doing their job as normal, rather than helping cancer.”

“We want to translate what we found into an intervention for patients, so that people who come with brain metastasis are treated with this. As a treatment for people who already have metastasis, it could work by ‘reeducating’ the astrocytes to do their job normally,” she said.

“It can also be used as a preventative measure, given to patients who have melanomas removed following surgery. This could prevent melanoma cells ever getting to the brain.”