This year, more than one million new cases of skin cancer will be diagnosed in the United States. Fortunately, if detected early, this potentially deadly condition is extremely treatable, averaging a cure rate of 95 percent. While current treatments for skin cancer involve treating or removing both cancerous and healthy skin, advanced research is producing new therapies which treat only the cancerous cells.

Speaking today at ACADEMY ‘06, the American Academy of Dermatology’s summer scientific meeting, dermatologist Hensin Tsao, M.D., Ph.D., F.A.A.D., assistant professor in the department of dermatology at Harvard Medical School in Boston, Mass., discussed emerging treatments for skin cancer.

“Cancer occurs when a normal cell in the body circumnavigates the normal growth checks and evades the immune system,” explained Dr. Tsao. “As technologies have advanced, it has become easier to identify cancer mutations, allowing us to better understand these growth signals and utilize this information to develop therapies that specifically target cancer cells.”

Targeted Therapies
Targeted therapies represent a new type of treatment against cancer. These therapies are able to detect the difference between cancer cells and “healthy” cells by targeting the genes or proteins that contribute to the development and growth of cancer. Several targeted therapies have recently received approval from the U.S. Food and Drug Administration (FDA) to treat cancer and research continues to develop more.

Targeted therapies were derived from a basic understanding of the cancer cell. In order for cells to grow, divide or die, they send and receive chemical messages. These messages are transmitted along specific pathways that involve various genes and proteins in a cell. “Genes that become mutated activate pathways which tell cells to proliferate,” described Dr. Tsao. “In other words, the traffic lights are always green and the brakes are frequently dysfunctional, so the cancer cell keeps multiplying.” Based on this information, research efforts are aimed at correcting or modifying pathways in a cancer cell.

“There are many benefits to utilizing targeted therapies to treat skin cancer,” said Dr. Tsao. “The primary benefit is that the mutations often reveal a weakness for that specific cancer and thus, a targeted treatment could be possible. A second benefit is that cancerous cells are specifically destroyed thereby sparing the healthy cells and minimizing side effects. This is a significant benefit over various forms of treatment that cannot distinguish between healthy and cancerous cells and therefore target both. Another benefit is that targeted therapies can be used for different types of cancer.”

Designing targeted therapies is a very complex process. Cancer cells have many forms of mutations in many different pathways. For a targeted therapy to be effective, it must target both the cancerous cell along with the specific pathways, which can be numerous. In addition, different mutations of cancer respond to different therapies. A therapy that may work in one patient with a specific form of cancer may not work in another patient with the same form of cancer. “The most challenging aspect of targeted therapies is that tumors can become resistant to a targeted treatment,” said Dr. Tsao. “Research continues to tackle these issues and each day brings us closer to finding answers.”

Immunotherapy
Immunotherapy uses the body’s own rejection system as a method of treatment. With certain cancers, especially melanoma, the immune system can play a significant role in monitoring the growth of tumors - moles can undergo complete regression as directed by the immune system. There are various forms of immunotherapy including cell transfer immunotherapy and topical immunotherapy.

Cell transfer immunotherapy is a treatment that uses the body’s natural defenses to fight the disease by stimulating the immune system to reject and destroy tumors. Studies have demonstrated that it can result in cancer regression in 50 percent of melanoma patients who do not respond to other treatments.

Topical immunotherapy was recently approved by the FDA for the treatment of basal cell carcinoma and actinic keratosis, the earliest stage in the development of skin cancer. A cream is applied to the skin every day for several weeks, helping to break down the lesion and regenerate healthy skin, essentially jumpstarting the body’s immune system to fight the lesion.

“Scientists are now attempting to harness the immunological benefits that appear to be effective against a small number of melanomas,” said Dr. Tsao. “While immunotherapy has not yet produced the types of responses hoped for by investigators, research continues to try to find effective immunotherapies.”

Stem Cells
“There is now some evidence that stem cells exist in cancers,” said Dr. Tsao. “Stem cells have the potential to divide without limit to replenish other cells, in this case, cancer cells.”

Stem cells respond to cells such as fibroblasts, or connective tissue cells, in the normal tissue, and they contribute to the development of an entire organ. As such, a more recent view of cancer is that the entire tumor mirrors the development of an organ. In this regard, new blood vessels are formed in a process termed angiogenesis, which is known to be a critical event in malignant transformation of skin cancer. During angiogenesis new blood vessels feed diseased tissues, destroy normal tissues and allow tumor cells to escape into the circulation and lodge in other organs causing tumor metastases.

“Research is trying to find therapies that will enhance cancer cell death, minimize invasion, diminish angiogenesis and increase the immune attack,” said Dr. Tsao. “The greatest potential lies with directing therapies against cancer stem cells.

“It is an exciting time in cancer biology and new emerging therapies will undoubtedly challenge the old views of cancer and hopefully offer more effective outcomes,” said Dr. Tsao. “The first step to effectively treat skin cancer is early detection. If a growth, mole, sore or skin discoloration appears suddenly, or begins to change, see a dermatologist to help you find the most effective treatment.”

American Academy of Dermatology