January 19, 2020

Israeli-German research team makes skin cancer breakthrough

Scientists in a collaborative Israeli-German research project say they have unlocked the secret of how melanoma spreads and are now able to point the way toward prevention of the killer disease.

Melanoma is the most aggressive and lethal type of skin cancer, causing the death of one person every 52 minutes, and scientists warn that global warming is likely increasing the number of cases.

The World Health Organization estimates that a 10 percent decrease in ozone levels will result in an additional 300,000 non-melanoma and 4,500 melanoma skin cancer cases yearly, and Israel’s Health Ministry says cases of the disease have doubled over the past three decades.

“We found that even before the cancer itself invades the skin, it sends out tiny vesicles containing molecules of microRNA. These induce the structural changes in the dermis, and prepares it for receiving and transporting the cancer cells to other parts of the body,” said Doctor Carmit Levy, the research leader at Tel Aviv University’s School of Medicine. 

“The danger does not come from the initial tumor that appears on the skin, but rather in its metastasis — cancer cells sent off to colonize in vital organs like the brain, lungs, liver and bones,” Levy said in an interview with the Journal.

The 25-member research team from the German Cancer Research Institute in Heidelberg, along with doctors and scientists from four Israeli universities and hospitals, used advanced microscopy tools to examine the interaction between the cancerous melanoma cells and the skin.

Their findings were published Aug. 22 in the prominent scientific journal Nature Cell Biology.

While the study published in that journal was subject to peer review, independent researchers have yet to weigh in.

The researchers said that by examining pathology samples taken from melanoma patients, the group was able to discover a central mechanism in the metastasis of skin cancer.

“To our surprise, we found changes that had never before been reported in the morphology of the dermis — the inner layer of the skin. Our next task was to find out what these changes were and how they related to melanoma,” Levy said.

Having mapped the cellular pathway melanoma cancer takes to spread to other organs, researchers began a quest to block it.

“This is a good example of how knowledge of the mechanism permits the identification of appropriate chemicals,” Dr. Jorg D. Hoheisel said in a telephone interview from Heidelberg, “All this work was a true collaboration between Tel Aviv University and our national cancer research center.”

The binational team identified two chemicals to stop melanoma.

A pair of selective inhibitors — SB202190 and U0126 — were found to retard the sprouting of the vesicles from the melanoma tumor to the skin and to prevent changes in the dermis even after the vesicles have emerged.

 “Although the mode of action is different, both chemicals inhibit the changes in the recipient cells in the dermis, which in turn affects the invasion of melanoma cells into the dermis,” Hoheisel said.

After successful lab tests with the two chemicals, the researchers believe these substances may serve as promising candidates for future drugs.

Despite the development of a range of melanoma treatments, including some successes in recent years in use of immunotherapy, no assured remedy yet exists for this life-threatening disease.

But German and Israeli scientists seem to disagree on the timeline to produce a pharmaceutical solution for melanoma. 

“What we generated is understanding, no cure,” Hoheisel said. “Unfortunately, it will be years before our findings may result in a benefit to patients.”

Levy is significantly more optimistic.

“We now have this amazing know-how on how melanoma spreads and even which chemicals can stop it,” Levy said. “We are enthusiastic that with these findings, the right funding and a good pharmaceutical partner, we can start testing experimental drugs within two years.”