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State of the Fight: Skin Cancer

Posted on May 30, 2012, 11:27 AM

Each month, in observance of the U.S. National Cancer Awareness Calendar, SU2C brings you The State of the Fight, a series of articles by those on the front lines of cancer treatment. We’ve asked our scientists to tease out myths from facts and report on breakthroughs in the field, as we all forge ahead in the fight to end this disease.

Margolin-Kim-5x7.jpgKim Margolin, M.D., is a professor of medicine in the Division of Oncology at the University of Washington and a member of the Fred Hutchinson Cancer Research Center, Melanoma Research Alliance (MRA) Medical Advisory Panel and MRA Grant Review Committee.

Skin cancer is the world’s most common cancer. Globally, between two to three million non-melanoma skin cancers and more than 132,000 cases of melanoma are diagnosed every year. In the United States alone, more than 76,000 cases of melanoma are diagnosed - one every eight minutes. Despite tremendous advances in medicine the melanoma death rate has remained static over the past 30 years, but the incidence is rising. This year alone, more than 9,000 Americans will die from the disease - one every hour.

These statistics are unsettling, but my hope and the hope of others in the cancer research community is that with new research and prevention methods we can change the odds and reduce the deaths from skin cancers.

Skin cancer is the uncontrolled growth of abnormal skin cells. There are three major types of skin cancer—basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and melanoma. BCC, the most common form of skin cancer, and SCC are easily treated with surgery when caught early, but can cause extensive damage to the surrounding tissue. These cancers, classified as non-melanomas, usually start in the basal cells or squamous cells found at the base of the outer layer of the skin. SCC occasionally proves fatal if it spreads to the lymph nodes or other organs; therefore, early detection remains important.

Melanoma, the most deadly form of skin cancer, develops from melanocytes. Melanocytes are cells that produce melanin, which is the pigment that gives your skin and hair their color. With early diagnosis and treatment, the chances of recovery are very good for patients with melanoma. If it is not found early, melanoma can grow deeper into the skin and quickly spread to other parts of the body. Once melanoma has spread beyond the skin, it is difficult to treat, and the median survival for Stage IV metastatic disease is less than one year. Melanoma represents just 4 percent of skin cancer diagnoses, but it is responsible for 80 percent of skin cancer deaths. A very rare type of cancer that arises in the skin and spreads quickly to other organs—Merkel cell carcinoma—occurs predominantly in immunosuppressed individuals and is not further addressed.

Surgery is currently the main therapy for all types of skin cancer. Different types of surgery may be needed, depending on the likelihood and pattern of the cancer and how much it has spread. Non-melanoma skin cancers generally stay localized and have a low chance of recurrence, so minor surgeries to remove the cancer are acceptable, and radiation therapy is generally reserved for cases where surgery would be impossible or disfiguring, such as certain parts of the face and in the case of large tumors. Melanoma, on the other hand, has high probability of both local and distant spread, so surgery often requires, whenever possible, a wide margin of uninvolved tissue around the tumor. In general, the prognosis of the very early stages of melanoma is somewhat less favorable than similar stages of non-melanoma, while in very advanced stages, both melanoma and non-melanoma can be lethal. 

Unfortunately in the last 20 years, surgery success rates for skin cancer have changed little.  Radiation therapy methods have improved a bit, but without major impact on outcomes, except for brain metastases of melanoma, which are more effectively controlled with stereotactic radiotherapy methods than with more traditional whole brain radiotherapy. However, the last year has seen major advances in treatment of advanced melanoma, in the form of two novel agents that work via very different mechanisms.  Vemurafenib works against melanoma that has a BRAF mutation (about half of the melanomas arising in skin) and leads to remission in the majority of patients. However, these remissions tend to last only about half a year on the average and are often followed by rapid tumor growth when the drug is stopped. The other agent, Ipilimumab, is a form of immunomodulation that profoundly stimulates immune responses and may provide long-term disease control in about 20 percent of patients. The risk of using this agent is that some patients may suffer immune-related toxicities due to the nonspecific nature of the immune stimulation which leads to an attack on normal tissues.

Both of the approaches for advanced disease are being further studied with newer agents that may provide better remission statistics and/or less toxicity to patients. Additionally, methods to safely combine these approaches and others that would inhibit the molecules responsible for the spread and establishment of metastases are all under investigation. 

As a physician, I have personally been involved in trials with the types of agents detailed above and others that may help increase the life expectancy of patients with advanced melanoma. One of my patients with widespread metastatic melanoma who did not respond to high-dose interleukin-2 and then to cytotoxic chemotherapy has had an excellent and very long-term remission using an investigational immunotherapy, PDL1 antibody, with very few side effects. This remission and excellent drug tolerance have allowed him to continue with a very high quality of life, which in his case means the parenting of teenage children, teaching Spanish fulltime in middle school, skiing and climbing mountains in Washington State on the weekends. Successes like these prove that we are making progress, but we still have much more work to do.

I was recently awarded a grant from the Melanoma Research Alliance (MRA), in partnership with Altor Biosciences and with the Cancer Immunotherapy Trials Network (of which I am one of the three principal investigators) to perform the first human clinical trial of a novel agent that has thus far shown a promising potential in animals. This molecule, known as ALT-803, combines an important cytokine (immune-modulating molecule that regulates immune responses) with its own receptor and with another portion of an antibody that further optimizes the body’s handling of this novel molecule.  It will first be tested in melanoma patients for safety and for its ability to stimulate immune cell numbers and responses to antigens. Our hope is that it will prove to be successful and alone or in combination with other therapy will lead to life-saving treatments for more patients suffering from this dreadful disease.

While some people are more susceptible to melanoma, everyone is at risk. Individuals who have fair skin, freckles, sunburn easily, have many moles, or have a family history of skin cancer have a higher risk for melanoma. Spending excessive amounts of time in the sun or living in sunny or high-altitude climates also increases your risk. No matter your skin type or geographic location, you should wear sunscreen and limit sun exposure to protect yourself from the sun’s damaging rays. Exposure to damaging UV rays from the sun and tanning devices is the most preventable risk factor for all skin cancers, including melanoma. To protect yourself daily from the sun’s rays: use broad-spectrum sunscreen (protects against UVA and UVB rays) with an SPF of at least 30 year-round, with frequent re-application, especially during sports (this is particularly important for children and for the whole family during all sunny-weather activities); wear sun protective clothing, hats, and sunglasses; seek shade; and avoid being out mid-day when the sun’s rays are most intense.

Another key to catching skin cancer in its earliest stages is to pay attention to any changes in your skin by performing skin self-examinations. Persistent sores that do not heal or raised pearly-red patches may be signs of basal cell carcinoma and squamous cell carcinoma. Melanoma can often appear as an irregular, multi-colored or changing mole. When giving yourself a skin examination, you should look for the A-B-C-D-E’s of melanoma. Moles or growths that are Asymmetrical, have an irregular Border, exhibit changes in Color, have a Diameter larger than the size of a pencil eraser (approximately 6 mm), or have Evolved in size or thickness . To identify the less concerning basal and squamous cell carcinomas, you should report to your doctor any pink spots that persist, recur in the same place over time, or are easily irritated. If you notice one or more of these signs, see your healthcare provider.

One of the best things you can do for yourself when it comes to skin cancer is to practice prevention, get educated, and establish a good relationship with your doctor. Taking advantage of free online resources available from the MRA, and the National Cancer Institute are great ways to stay informed on the most recent findings in skin cancer research and prevention. With this kind of knowledge, if you or a loved one receives a skin cancer diagnosis you will be armed with the tools to help you create a great medical team and treatment plan. We have so far to go in skin cancer research but we are making great efforts to find a cure for this, all to often, deadly disease.

Stand Up To Cancer has also partnered with the MRA to create a Melanoma Dream Team focused on using next-generation sequencing technology to examine both the normal and cancer genome of patients with metastatic melanoma. Patients whose melanoma tumors do not have BRAF alterations will have other specific genetic alterations identified and these changes will be matched to an appropriate therapy that directly targets those alterations. The hope is that this “personalized medicine” approach will lead to more effective and lasting treatments and potentially spare patients from unnecessary treatments that are expensive, highly toxic and all too often provide little or no benefit.

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