Blocking Out Skin Cancer

Dr. Madeleine Duvic (standing) works with research associate Dr. Parul Hazarika in studying the causes of skin cancer.

Skin cancer represents an urgent challenge for more than 50 M. D. Anderson scientists, who are expanding their efforts to improve the control of this common disease.

Some sobering statistics illustrate the importance of picking up the pace in research that should provide more successful treatments and effective prevention strategies:

· Skin cancer is the most prevalent type of cancer in the United States.

· One in every three cancers diagnosed each year in the U.S. is a skin cancer.

· Increasing incidence of skin cancer indicates that almost one-half of all Americans will have skin cancer by age 65.

"The two goals of our Skin Cancer Research Program are to accelerate our understanding of the biology of skin cancer and to apply this new knowledge to designing better prevention and treatment tactics," explains Dr. Margaret L. Kripke, chairman of the Department of Immunology and director of the interdisciplinary research initiative.

Dr. Kripke anticipates the newly focused close collaboration of faculty from a dozen different basic science and clinical disciplines will allow these goals to be attained more rapidly and efficiently than previous projects that did not fully integrate research interests and investigations in a programmatic way. She also cites two motivating components for such an ambitious program. The first is geography; the second is the cancer center's mission.

"Exposure to ultraviolet radiation (UV) from the sun and skin type are the primary factors influencing development of the vast majority of skin cancers," says Dr. Kripke, who holds the Vivian L. Smith Chair in Immunology. "Texans and people in other southern states typically receive excessive UV radiation because of our proximity to the equator and propensity for outdoor work and recreational activities. Many of these people are light-skinned, making them more vulnerable to sunlight-induced damage.

"As a public institution whose mission is to eliminate cancer as a significant health problem, M. D. Anderson has the unique opportunity - and the responsibility - to reduce the severe toll that skin cancer now takes," she adds.

Improving molecular techniques should help researchers better understand the mechanisms of skin cancer formation and growth, the reasons why some skin cancers spread to other body sites, and the role of immunology and genetics in patients' responses to therapy. Research is targeted at the following skin cancers:

· Basal and squamous cell carcinomas, the most common type.

· Melanoma, the most deadly form.

· Cutaneous T-cell lymphomas, a relatively rare but seldom cured skin cancer that, like melanoma, is increasing rapidly.

New basal and squamous cell skin cancers will be diagnosed in more than 900,000 Americans this year. While highly curable, these skin cancers frequently occur on the face and hands where surgical removal may be difficult and disfiguring. Dr. Kripke notes, "The cosmetic, psychological, emotional and financial burdens of these skin cancers can be enormous even when the disease is not life-threatening."

Multiple projects combining laboratory and clinical data aim to understand the molecular events that lead to formation and growth of the common skin cancers and to assess new treatments for preventing regrowth after surgery to remove the tumors. A key faculty leader involved in these projects is Dr. Helmuth Goepfert, head of the Division of Surgery ad interim, chairman of the Department of Head and Neck Surgery, and holder of the M. G. and Lillie A. Johnson Chair for Cancer Treatment Research.

Unlike other skin cancers, melanoma has the potential to reach the bloodstream and invade internal organs fairly early. Once this happens, it is usually fatal. Dr. Antonio C. Buzaid, medical director of the Melanoma and Skin Center, and several colleagues from diverse fields are extending research to:

· Discover the biological and molecular characteristics that will explain why different thicknesses of melanoma cells are more aggressive and prone to spread, and to develop diagnostic methods to identify patients at highest risk for metastasis so they can be treated more aggressively.

· Determine why biochemotherapy, which combines anti-cancer drugs with drugs that boost the immune system, works well for some patients and not others; to evaluate techniques for use in the operating room to detect melanoma cells that have spread to lymph nodes; and to deliver powerful drugs directly to recurrent melanomas in the arms or legs.

In addition, Dr. Kripke and her core research group have extended their fundamental studies of the role excessive UV radiation plays in injuring the immune system, which in many parts of the world may be a more serious problem than causing skin cancers. In animal studies, UV-induced immunosuppression can increase susceptibility to infectious diseases, escalate the severity of infections and delay recovery from them. Ultraviolet radiation damage to the immune system can occur in people with all skin colors, too.

Another promising area investigated by her team focuses on how well sunscreens protect the skin. Previous animal studies suggest that sunscreens may give "a false sense of security since they can protect against sunburn but may still allow other forms of photodamage, such as immune system impairment and skin aging," Dr. Kripke says.

Recent research has shown that UV radiation can induce mutations in the p53 tumor suppressor gene that normally helps prevent skin cancer development. This genetic change took place in the mice being evaluated long before tumors appeared, but SPF-15 sunscreen applied before each UV radiation exposure nearly abolished the p53 mutations.

Dr. Madeleine Duvic, professor of medicine and chief of the Section of Dermatology, coordinates many of the services for patients with basal and squamous cell skin cancers and heads the clinical research concerning cutaneous T-cell lymphoma (CTCL), also known as mycosis fungoides. It is a disease in which some immune system cells become malignant and affect the skin. Although the least common form of skin cancer, the incidence of CTCL has doubled in the last 20 years and is still rising.

"Unlike other skin cancers, we don't know what causes mycosis fungoides. Theories include exposure to petrochemicals, pesticides, other environmental toxins and possibly a virus. It often looks like such skin problems as eczema or psoriasis, so it may be ignored or misdiagnosed. A skin biopsy is the only way to confirm it," Dr. Duvic explains.

Virtually all patients treated for CTCL at M. D. Anderson participate in clinical trials that include evaluations of anti-cancer drugs, synthetic vitamin compounds called retinoids, radiation therapy, a special type of light therapy, topical gels containing retinoids, biologic agents like interferon and using lasers to resurface the skin. A potential new technique will involve molecular gene therapy, in which a vaccine could be made for each patient.

In her primary laboratory at The University of Texas-Houston Medical School, Dr. Duvic analyzes human skin samples to determine the underlying genetic and immunological components that influence development of CTCL.

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