Israeli research team unlocks the secrets of a deadly cancer

By Cindy Mindell

In recent years, the State of Israel has emerged as a powerhouse in the field of medicine, with Israeli ingenuity producing a stream of innovative medical advances.

Now, in another breakthrough, a Tel Aviv University research team led by Dr. Carmit Levy has just revealed how melanoma behaves at deeper levels of the skin, a finding that may provide a cure for the lethal skin cancer.

Melanoma is known as the deadliest form of skin cancer, responsible for approximately 80 percent of skin cancer-related deaths. The cancerous growths develop when unrepaired DNA damage to skin cells – most often caused by ultraviolet radiation from sunshine or tanning beds — triggers mutations that lead the skin cells to multiply rapidly and form malignant tumors. Melanoma occurs in both younger and older people, although rates increase with age and are highest among those in their 80s.

But it is also one of the more common cancers in young adults, especially young women. According to the New York-based Skin Cancer Foundation, a 2012 study of young adults aged 18 to 39 in Olmstead County, Minn. reveals an alarming rise in melanoma over the last 40 years, with rates growing by 800 percent among young women and 400 percent among young men. A recent article in the journal Nature reinforces the findings of an earlier genetic study linking ultraviolet rays to melanoma.

Israel is proving to be a leader in melanoma research and treatment. Just this month, in addition to Levy’s breakthrough, researchers in Israel, the U.S., and several European countries showed that a combination of two existing immunotherapy drugs can dramatically reduce melanoma tumors.

Dr. Levy, a Jerusalem native of Yemenite heritage, earned graduate degrees in pharmacology and biochemistry from the Hebrew University of Jerusalem Hadassah Medical School and completed post-doctoral studies at Harvard Medical School before establishing her own lab at Tel Aviv University in April 2011. As a member of the Department of Human Molecular Genetics and Biochemistry at the university’s Sackler Faculty of Medicine, Levy studies the role of microRNAs in the development, differentiation, and transformation of skin cells into malignant cancer cells, with the goal of developing novel approaches to the prevention, diagnosis, and treatment of skin cancer in general and melanoma in particular. Levy’s work is supported by a grant from the Israel Cancer Research Fund (ICRF), the largest North American charitable organization solely devoted to raising private funds for cancer research in Israel. Founded in 1975, ICRF has provided more than $50 million in grants to more than 2,000 researchers in Israel.

Levy will present her groundbreaking discovery this month at two ICRF-sponsored talks in Connecticut.

She spoke with the Ledger about what her findings may mean for the future of melanoma treatment.

Q: What is unique about your melanoma research?

A: We are following melanoma in stages, step by step, as it travels from the lower level of the skin – the epidermis – down into the dermis. So, we are tracing the very first steps of melanoma development and the more radical stage in melanoma development, when it emerges or invades from the epidermis to the dermis. This is the critical or fatal stage because in the dermis, melanoma is meeting blood vessels and blood vessels immediately mean that cells can spread and metastasize, and people die from metastasis. Many cancer researchers are doing research for metastasis and treating the patient after; we are dealing with it at the very beginning.

We have two stories. The first one is about the triggers that push melanoma to invade, switching from radial growth staying at the epidermis – which I would call the “safe mode” of melanoma. This is the state where, if it is caught and removed, the patient is usually safe; the cells did not invade the dermis. We discovered a trigger for the cells to move down and we are working on a patent for a drug to prevent this trigger to be active and therefore keeping melanoma on the surface. This research was just accepted for publication in a very high-profile journal so I’m very excited.

In the second story, we are following melanoma right after entering the dermis, when melanoma then needs to find its way to the vein. Once entering the dermis, what happens until melanoma meets the vein? If we miss blocking melanoma invasion, maybe we can block melanoma proliferation of the dermis until it reaches the vein.

We discovered how melanoma communicates, by sending small vesicles [a small fluid-filled cyst within the body] to the dermis prior to invading and preparing the dermis for its arrival, which makes it more aggressive. We are offering a drug, not yet patented, and I’m going to show data about it.

Q: How does your research differ from how melanoma is typically addressed?

A: Usually, when dermatologists diagnose melanoma or something suspicious on the skin, they look at the pathology and for two things: scars at the dermis, which will indicate that there was more severe melanoma in the past that is now gone; and to check exactly how many millimeters melanoma invaded into the dermis. If they see no invasion or scar, they don’t recommend treatment of lymph nodes. However, what we discovered is that, if I take those biopsies indicating that melanoma hasn’t invaded yet and there is no scar, we look at these patients and consider them “safe,” but we discovered that the dermis has in fact been changed. There are small changes in the dermis and we discovered what they are and we can say now that the dermis is preparing for the arrival of melanoma.

Q: What are the known causes of melanoma and what are some viable prevention measures?

A: The two major factors are people who show a clear correlation between sun exposure at a young age and melanoma, and genetics.

Not all sunscreens block all types of UV rays. The dangerous age of being exposed to the sun – with and without sunscreen, and I’m not recommending using sunscreen and going into the sun to cook yourself – is until age 13. After age 13, going into the sun is about getting wrinkles and other kinds of skin cancer considered less deadly than melanoma. So, if it’s possible, parents should keep kids out of the sun or have them wear long sleeves. Regarding sunscreen, there is research that is not mature yet, talking about the different types of melanin in the skin: we have two types, and sunscreen tends to change this balance.

Red-haired people are in a high-risk group, and if there is any history of melanoma in the family, I would recommend protecting yourself and not trusting sunscreen. People of color tend not to get skin cancer but there are rare cases like Bob Marley, who died of melanoma. Check your family history; it’s all there in the genes. If you are in a high-risk group, you need to have to have your skin regularly checked for moles.

Q: Is there anything specific to Israel – climate, population, etc. – that is particularly valuable in melanoma research?

A: Doing research in Israel in general is very unique. People are very helpful and accessible and there is a lot of brainstorming. I can just pick up the phone and call friends and one will give me advice on RNA and another will give me advice on a specific drug delivery. You don’t have to make a big deal of organizing a meeting; people are willing to help you on the spot.

Dr. Carmit Levy will discuss “Latest Breakthroughs in Malignant Melanoma and Other Cancers in Israel” in Connecticut on Sunday, June 14, 11 a.m. at a private home in West Hartford; and Tuesday, June 16, 7 p.m. at a private home in Danbury. Levy’s visit is sponsored by the Israel Cancer Research Fund. For reservations call (203) 321-1006. For information contact David Kweskin, ICRF Connecticut area director, at David.Kweskin@ICRFonline.org.