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In Rare Skin Cancer, Virus Emerges as Target and Tool

Posted May 17 2011 10:19pm

In Rare Skin Cancer, Virus Emerges as Target and Tool

George Campbell, a Merkel cell cancer patient. (Photo courtesy of George Campbell) George Campbell in May 2005. A small bump on his left forearm would later be diagnosed as Merkel cell cancer. (Photo courtesy of George Campbell)

In the spring of 2005, George Campbell was vacationing with his wife in California when he noticed a bump on his left arm. The bump was colorless and painless, but it had not been there before. When the 57-year-old U.S. Air Force retiree returned home to South Carolina, his doctor lanced the growth, and Campbell hoped that would be the end of it.
 
But a month later, the bump was four times its original size. The doctor then removed the growth and some skin around the area. After eight pathologists analyzed the tissue, Campbell received a diagnosis: Merkel cell carcinoma (MCC), a rare but aggressive form of skin cancer.

This disease tends to occur in people who have compromised immune systems and in older people. Tumors often develop in sun-exposed areas of skin, and UV radiation is a possible risk factor. Approximately 1,600 people in the United States are diagnosed with MCC each year.

Like many patients with MCC, Campbell could not find a local oncologist with experience in treating the disease. So he traveled to Boston, where Dr. Paul Nghiem, then at the Dana-Farber Cancer Institute, and other experts developed a treatment plan. Two weeks later, Campbell underwent surgery, and he has been free of cancer since.

"I am one of the fortunate ones," said Campbell. "Because the cancer was caught early, I fell into the 10 percent of cases that have a low chance of recurrence ." Nearly half of all patients with this often fast-growing cancer survive less than 5 years after diagnosis.

Rapid Advances in Research

A new understanding of MCC has emerged since 2008, when researchers discovered a previously unknown virus in 8 of 10 tumors. The finding has been confirmed by many groups, and the virus is now implicated in most—but not all—cases of the cancer.

An electron microphotograph of Merkel cell polyomavirus virus-like particles.An electron microphotograph of Merkel cell polyomavirus virus-like particles .

"In the last 3 years, cancer biologists have turned this disease upside down," said Dr. Patrick Moore of the University of Pittsburgh Cancer Institute, who, with his colleague Dr. Yuan Chang, co-led the team that discovered the virus, now called Merkel cell polyomavirus (MCV).

"When you find a virus that is really causing cancer, the pace of research moves fast," noted Dr. Moore, whose team also discovered the virus that causes Kaposi sarcoma in 1994. "Every new piece of data provides a way of looking at the complex picture of how viruses can cause tumors."

Most people are infected by MCV as children, but the virus causes cancer only rarely. A series of molecular events must occur for tumors to develop, and each of these events is rare. The first step is likely to be the loss of immune control over the virus, Drs. Chang and Moore noted in a recent article on viruses and cancer.

Experimental Blood Test Detects Recurrence

Understanding how a person's immune system responds to the virus could lead to new diagnostic tools and, potentially, treatments. Now at the University of Washington, Dr. Nghiem and his colleagues have developed an experimental blood test that, in a small number of patients, identified a recurrence of the cancer before the disease was clinically detectable.

The test allows researchers to monitor levels of antibodies that a patient produces in response to proteins (antigens) in the virus. These levels tend to fluctuate with the extent of the cancer, falling after treatments and rising with recurrences, the researchers reported last year.

In a recent case, the test showed that a patient's antibody levels were slightly above baseline, though the man felt fine. He had an imaging test, which revealed a mass. "Because of the test, doctors will be able to treat the cancer earlier than they otherwise might have," said Dr. Jayasri Iyer, a research fellow working with Dr. Nghiem.

"The immune response provides a unique window into the disease," said Dr. Nghiem. "We are not aware of another cancer that can be detected via an immune response against tumor antigens." The test needs to be validated in a larger study, he added.

Moving Toward Immune-Based Treatments

In separate work, Dr. Nghiem and his colleagues recently identified a factor that may help explain why some patients fare better than others. Patients whose tumors were infiltrated by immune cells had better outcomes than patients whose tumors were not.

"This tells us that the body's ability to mount an immune response into the tumor is important in determining the outcome and survival in these cases," Dr. Nghiem said.

These findings appeared recently in the Journal of Clinical Oncology with a companion report on MCC. Both studies concluded that immune "readouts" from patients infected by MCV may contain prognostic information.

The studies also "provide more evidence that MCV plays a causal role in this cancer," said Dr. Christopher Buck of NCI's Center for Cancer Research , who co-authored an accompanying editorial with Dr. Douglas Lowy, chief of CCR's Laboratory of Cellular Oncology and deputy director of NCI.

What's more, Dr. Buck continued, the studies provide hope that the human immune system one day could be recruited to help clear tumors in some patients. "Viruses do cause some cancers, but the good news is that a virus can often be a tool in your arsenal for treating the disease," he said.

Dr. Moore agreed. "Now that we know the tumor is caused by the virus, we can look for ways to stimulate virus-specific immunity," he said, noting that his group and others were working on the approach.

For Patients, New Diagnostic Codes

Although immune-based therapies could be years away, patients with MCC have benefited from recent changes in how this disease is reported by doctors. New diagnostic codes that are specific to MCC were approved in 2009. Insurance companies often use these codes in making decisions about coverage.

Under the old codes, MCC was grouped with less aggressive skin cancers that do not require the same extensive tests and imaging studies. Consequently, patients have been denied coverage for tests their doctors ordered.

"The new codes have made a big difference," said Dr. Iyer, who co-led the effort to develop them. "Not only can patients get approval for care from insurance companies, but researchers can now track [the incidence of] MCC more easily."

Connecting Patients with Experts

Dr. David Schuster Dr. David Shuster has blogged about his " battle with Merkel cell cancer " since last year.

Another difference over the last few years has been the increasing use of the Internet as a way for people with rare diseases to share experiences and information. Back in 2005, when George Campbell was recovering from surgery, he decided to create an online discussion and support group for people affected by MCC. Though he initially wondered whether anyone might want to join, the group now has more than 460 active members around the world.

The support group has helped many newly diagnosed patients find experts on the disease; one such patient was Dr. David Shuster, a 70-year-old diagnostic radiologist from California. After he was diagnosed with MCC a year ago, his son discovered the support group and was put in touch with the closest expert, Dr. Nghiem.

A few weeks later, Dr. Shuster flew to Seattle and developed a new treatment plan with the doctors there. He then returned home to receive radiation therapy from his local doctors under Dr. Nghiem's supervision.

The treatment helped, but the disease has recurred twice. Earlier this month, after considering his options, Dr. Shuster started chemotherapy. Support from people on the listserv and readers of his blog, My Battle with Merkel Cell Cancer , has been a comfort, he said.

"When I decided to go ahead with chemotherapy, I thought it might just postpone the inevitable, or just make me sick," he said in an interview. "But there are anecdotal reports from people in the support group who've had chemotherapy alone and survived for years. That gives me hope."

Edward R. Winstead

For more information visit NCI's Web page on MCC

To find the discussion/support group, search Google Groups for "Merkel Cell Cancer."

    

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