UNM Cancer Center Scientists Unravel Melanoma’s Mysteries

Posted on August 2nd, 2011 by msequeira

New research is changing the face of melanoma detection, treatment and prevention

In this high-desert city, UV radiation is intense year round—but especially during the summer, when Albuquerque’s UV index regularly tops out at 11+, the highest level measured. Melanoma, the least common but deadliest form of skin cancer, is strongly linked to UV exposure. Not surprisingly, New Mexico has one of the highest rates of melanoma in the nation: approximately 320 new cases are diagnosed in the state each year, and around 49 people die of the disease. Melanoma is one of the most common cancers among young people, and is actually a leading cause of cancer death among young women aged 25 to 34. Disturbingly, the disease is on the rise: melanoma incidence has more than doubled since 1975, according to the NM Department of Health. Caught early, many melanomas can be treated successfully through surgery. Once melanoma has spread beyond the skin to other areas of the body, however, treatment options are limited and survival rates plummet.

 

Scientists at the University of New Mexico Cancer Center are changing how we understand, detect, treat and prevent the disease. Marianne Berwick, PhD, MPH, co-leads the Cancer Population Sciences Program at the UNM Cancer Center. An internationally recognized melanoma researcher, she is also Associate Director for Population Sciences and Chief of Epidemiology in the UNM Department of Internal Medicine. In recent years, her work has focused on the interaction between genes and the environment. Certain genes—such as a pigment gene associated with red hair—are known to increase a person’s risk for melanoma. But so far, the correlation between genes and melanoma risk seems to be relatively weak, and Dr. Berwick says she is more interested in identifying those genes involved in aggressive melanoma versus more mild, so-called “indolent” forms of the disease. Distinguishing between the two is a key step in better understanding melanoma and in developing more effective treatments.

 

Melanoma is a disease of the melanocytes, one of two major types of skin cells. (Keratinocytes, the other major skin cell type, is responsible for squamous and basal cell carcinomas, very common and less lethal forms of skin cancer.) How and why melanoma develops is not fully understood, says Dr. Berwick. “Certainly, sun exposure—especially the ‘blast of sunshine’ that people who work indoors receive on the weekend or on vacation—is a major factor,” she says. “Sun exposure will help you get melanoma—that’s for sure. But there are genetic, immune function and other factors at play that determine how susceptible you are and how aggressive your melanoma is. This is a complex disease.”

 

Lowering your melanoma risk

Still, there are essential steps that people can and should take to lower their melanoma risk. The most important is to be “sun smart.” What does this mean? Dr. Berwick explains that effectively protecting yourself from the sun requires more than rubbing in a bit of sunscreen and heading out the door. “Sunscreen can be useful, but it’s not a cure-all,” Dr. Berwick cautions. “It can even be harmful if it leads people to spend more time in the sun than they otherwise would.” Long, loose clothes, wide-brimmed hats and UV-blocking sunglasses are the best forms of protection. Sunscreen with an SPF of 15 or higher is a useful complement to these. When you apply it, use much more than you think you need, says Dr. Berwick; otherwise, you’ll only be getting a fraction of the indicated SPF. Avoiding the sun between the peak hours of 10am and 4pm is also a wise move. Another step to lowering your risk? Do not tan indoors. A recent large study by Dr. Berwick and colleagues found that young adults who use tanning beds have an almost threefold risk of melanoma.

 

No one is immune from melanoma, though people with light skin and eyes are at greater risk. These people in particular should perform monthly full-body skin exams. A new spot or one that has changed in size, shape or color should be checked out by a doctor. There is some evidence to suggest that greater awareness of melanoma is leading to earlier detection, one key to improving outcomes. (Earlier detection may also partly account for rising melanoma rates, Dr. Berwick believes.)

 

One survivor’s story

Detection can be as simple as noticing something that’s “not right”—and taking action. Melanoma survivor and Albuquerque resident Ellen King says she owes her life to an observant and persistent hairdresser. King, co-owner of Bradbury Stamm Construction with her husband Jim, was diagnosed with melanoma 11 years ago, after her hairdresser noticed a suspicious spot on her scalp and urged her have it checked by a doctor. When King’s first doctor assured her the spot was harmless, the hairdresser pushed King to seek a second opinion. King did, and she was diagnosed with melanoma shortly thereafter.

 

Fortunately, the disease had not metastasized, and King was successfully treated. Today, she remains cancer-free—and passionate about the cause of melanoma awareness and prevention. She generously supports research at the UNM Cancer Center, helping to fund the collection and banking of tumor tissue and DNA samples, both of which are essential raw materials for melanoma research. “Ellen’s funding is absolutely the backbone of our work,” says Dr. Berwick, citing the tissue bank’s role in a current collaboration with the University of Colorado involving the identification of melanoma stem cells, which may determine how aggressive a tumor is. Other work for which tissue samples are a critical resource includes a project investigating the ostensible female “survival advantage” in melanoma; this research is looking for a possible correlation between melanoma survival and certain estrogen receptors on the melanoma cell surface.

 

A new approach to diagnosis and treatment

Meanwhile, another UNM Cancer Center researcher, Yubin Miao, PhD, Assistant Professor of Pharmaceutical Sciences at the UNM College of Pharmacy and a specialist in radiopharmaceuticals, is pioneering a promising new method for diagnosing and, eventually, treating melanoma. His approach uses a specially modified class of peptides with a high binding affinity for protein receptors called MC1 that are commonly overexpressed in melanoma cells. (The chemical modification of the peptide is itself a remarkable achievement; the sequence of amino acids that Dr. Miao and his team have created is unique, and Dr. Miao has filed for a patent to protect the discovery.) Tagged with a radioisotope to allow for imaging detection and then released into the bloodstream, these “radiolabeled” peptides bind selectively to melanoma cells and emit a signal that precisely identifies the malignant cells’ location. Imaging equipment such as SPECT/PET collects these signals and generates a series of pictures that show exactly where melanoma cells reside within the body.

 

This new diagnostic method has been tested successfully in animal models, and Dr. Miao hopes to bring his innovation into human clinical trials in the next few years. He believes it will prove particularly powerful as a diagnostic tool for melanoma in the early stages of metastasis. The current method for imaging metastases uses a glucose-related radiopharmaceutical that is not a cancer-specific agent, but rather identifies cells that have a high glucose uptake. “While this is true of many cancer cells, not all use glucose as a direct energy resource,” explains Dr. Miao. “Moreover, the existing approach does not reliably detect very small metastases.” Because the new radiolabeled peptides have a high binding affinity for melanoma cells, they promise to accurately image even very early metastases—an essential step toward improving outcomes for patients whose melanoma has just begun to spread through the blood or lymph systems to other areas of the body.

 

In addition to their imaging potential, Dr. Miao’s radiolabeled peptides also show promise as the basis for new methods of treating metastatic melanoma. Such methods are urgently needed because, as noted above, current treatments are only modestly effective at slowing the disease, and no curative treatments exist. (Melanoma is somewhat resistant to conventional chemotherapy, though a couple of new chemotherapy drugs for advanced melanoma came onto the market this spring—the first drugs for metastatic melanoma approved by the FDA in over a decade.) By exchanging the imaging agent for a therapeutic one, Dr. Miao would seek to “retool” the peptides to deliver small, precisely targeted doses of radiation directly to melanoma cells, leaving the rest of the body’s cells unharmed. Clinical applications of the radiolobeled peptides

 

to melanoma treatment are still years down the road. But for a disease that has proved especially hard to treat, even by cancer’s standards, this new therapeutic direction is a source of excitement and hope among melanoma researchers.

 

Putting the pieces together

Dr. Miao and Dr. Berwick are just two of numerous scientists engaged in melanoma research at the UNM Cancer Center. Other key projects include a study by Laurie Hudson, PhD, Regents’ Professor of Pharmaceutical Sciences, examining how melanocytes respond to arsenic exposure (a suspected risk factor for melanoma), and work by Graham Timmins, PhD, Associate Professor of Pharmaceutical Sciences, who was recently awarded a patent for a new method for measuring DNA damage in the skin resulting from UVA exposure. With these and other efforts, the puzzle of melanoma is slowly being pieced together, and all New Mexicans—disproportionately at risk in one of the nation’s sunniest states—stand to benefit.

 

About the UNM Cancer Center

The UNM Cancer Center is the Official Cancer Center of New Mexico and the only National Cancer Institute (NCI)-designated cancer center in the state. One of just 66 NCI-designated cancer centers nationwide, the UNM Cancer Center is recognized for its scientific excellence, contributions to cancer research and delivery of medical advances to patients and their families. It is home to 85 board-certified oncology physicians representing every cancer specialty and 127 research scientists hailing from prestigious institutions such as MD Anderson, Johns Hopkins and the Mayo Clinic. The UNM Cancer Center treats more than 65 percent of the adults and virtually all of the children in New Mexico affected by cancer, from every county in the state. In 2010, it provided care to more than 15,800 cancer patients. The Center’s research programs are supported by nearly $60 million annually in federal and private funding.

 

UNM Cancer Center contact information
Dorothy Hornbeck, JKPR, (505) 797-6673, dhornbeck@jameskorenchen.com
Audrey Manring, UNM Cancer Center, (505) 925-0486, amanring@salud.unm.edu

 

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Tags: Melanoma, research program, Screening/Prevention Melanoma

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