Researchers can more easily set their sights on targets for new treatments for the deadliest skin cancer, thanks to landmark findings by UCSF Comprehensive Cancer Center member Boris Bastian, MD, PhD, and colleagues. The findings also argue against earlier research — controversial and well publicized –which suggested that sun exposure is not a major risk. Bastian’s research indicates that the bottom line remains unchanged — sun exposure is bad if you want to lessen your chances of dying from the deadliest skin cancer. The skin pathologist and his colleagues showed that the skin cancer known as melanoma comes in at least four distinct varieties. The different types may require different targeted therapeutic approaches, the researchers found. Bastian and colleagues classified melanomas in a new way. The classification was based on body sites where cancers arose and on degree of sun exposure. The researchers discovered marked differences in the way genes were altered among the types. Different biochemical pathways tend to be disrupted in the different types of tumors identified. This new knowledge should make it easier for pharmaceutical researchers, who can develop new drugs to better target these distinct tumors and their genetic abnormalities. Melanoma has been notoriously difficult to treat. That’s because it is diagnosed late and drugs are ineffective. The death rate from the disease has changed little in two decades. Sunlight is a major risk factor for two of the types of melanomas, Bastian asserts. For the other types, it is less important. Researchers estimate accumulated sun exposure by measuring the degree to which skin has undergone solar elastosis — a breakdown of elastic fibers associated with aging skin and wrinkles. According to Bastian, the genetic abnormalities found in melanomas that tend to arise on sites with less sun exposure — such as the trunk, arms or legs — differ from melanomas that arise on chronically exposed skin, such as the face. Bastian and colleagues found that they could accurately separate these two types of cancer from each other 84 percent of the time. They did this simply by comparing chromosomal abnormalities. Two other, rare forms of melanoma that arise on sites rarely or never exposed to sun also can be distinguished from each other with similar success using genetic criteria, Bastian and colleagues found. The lumping together of all melanomas has led to confusion and controversy. “The monolithic view of melanoma has made it next to impossible to develop an integrated view of the role of UV light,” Bastian says. “The finding of other investigators that melanomas on chronically sun-damaged skin have a better prognosis is now easier to explain, considering that these melanoma types are genetically and biologically different from one another,” he says. Bastian disagrees with the proposition that this prognostic difference indicates a beneficial role for UV exposure.