Dark Side of the Sun

Did you know that skin cancer is the most common form of cancer in the U.S? And that it's been on the rise for more than 30 years? In fact, the American Cancer Society estimates that, in 2014, more than 76,000 new melanomas will be diagnosed in the U.S. alone, and over 9,700 people will die of the disease.

Prevention – such as wearing a high-SPF sunblock anytime we go outside, even on overcast days – and early screening are critical, because fighting skin cancer once it develops can be difficult, even impossible. That's why the Weizmann Institute of Science is investigating skin cancers from a number of angles:

Identifying the genetic mutations that cause melanoma. Prof. Yardena Samuels, who headed the National Human Genome Research Institute's Molecular Cancer Genetics Section, part of the U.S. National Institutes of Health, before joining Weizmann, uses the power of DNA sequencing to identify new groups of genetic mutations involved in melanoma, the deadliest form of skin cancer. In fact, one of her discoveries, a mutation found in nearly one-fifth of melanoma cases, inspires particular hope because it is located in a gene already targeted by a drug approved for some types of breast cancer. Preliminary clinical trials are underway. Read more.

How does melanoma survive toxic treatments? In the lab, drugs can destroy melanoma cells and those of many other cancers, but have limited efficacy in patients. How is cancer able to survive today's potent treatments? Dr. Ravid Straussman, who joined Weizmann in 2013, made a surprising discovery during his postdoctoral research at the Broad Institute of Harvard and MIT: Normal cells residing within a tumor may actually help cancer cells grow and survive anti-cancer drugs. This is a new, underexplored area; fortunately, Dr. Straussman is studying the fast-growing melanoma to identify the biological basis of this drug resistance.

Thinking opposite to fight melanoma. In order to live, a tumor must attract fresh blood vessels – a process called angiogenesis – to obtain oxygen and nutrients and remove waste. In fact, therapies that stop angiogenesis have aided patients with some cancers, but not melanoma. An alternative treatment, immunotherapy, recruits immune system cells called CTLs to fight cancer cells. New CTL drugs have helped melanoma patients; however, immunotherapy requires constant oxygen – which also makes tumors grow. Dr. Guy Shakhar is studying this paradox, finding that the treatment of melanoma could be improved by enhancing, rather than restricting, oxygen supply to tumors.

Melanomas get stressed, too. As stated above, solid tumors require angiogenesis to grow. Conversely, a lack of new blood vessels can lead to necrosis: cell stress and death due to insufficient nutrients. Prof. Menachem Rubinstein studies how tumor cells regulate stress, focusing on the endoplasmic reticulum (ER), a cellular organelle in which proteins are synthesized. In seeking to understand how melanoma cells stay alive despite extensive ER stress due to nutrient shortage, he found a protein that promotes melanoma growth, but not in the usual ways; rather, it's by helping the cancer cells withstand such stress, thus reducing death by necrosis. This discovery reveals a new pathway that melanomas use in order to thrive – and possibly a new way to fight them.