Bioscience

Mayo surgeon fights cancer in both lab and OR

April 16, 2004

By Flinn Foundation

While a cure for cancer continues to elude the world’s leading medical researchers, Dr. Barbara Pockaj, a surgical oncologist at Mayo Clinic in Scottsdale, feels she is curing cancer every day in the operating room, one tumor at a time.

“It’s rewarding to see the most immediate impact on peoples’ lives,” Pockaj says.

But her greatest contribution could ultimately come not in the OR, but the laboratory.

Pockaj plays a key role in an extensive Arizona research collaboration focusing on melanoma, the most serious form of skin cancer and a concern that resonates strongly with residents of the desert Southwest.

Pockaj is head of the melanoma disease site team at Mayo involved in the collaboration of more than 30 investigators from, Arizona State University, the University of Arizona, and the Translational Genomics Research Institute (TGen).

“Opportunities for the prevention, surveillance, and treatment of patients with melanoma are being planned with clinical investigators and population scientists at Mayo and the UA,” says Dr. Laurence J. Miller, director of Mayo Clinic’s Cancer Center.

“The Arizona Bioscience Roadmap effort has identified skin cancer as one of the unique opportunities in the state,” Miller said, referring to the Arizona’s long-term strategy to advance its biosciences industry. “All of these institutions, and others, are at the table and are exploring ways to work together to serve this effort optimally.”

Pockaj is also a co-investigator on one of the first grant applications submitted as part of this larger collaborative effort. Along with Michael Bittner at TGen and Frederick Zenhausern at ASU, she submitted a proposal to the National Institutes of Health for funding to use microarray technology to predict patient response to interleukin-2 therapy for metastatic melanoma.

 

A ‘surgical personality’

Pockaj maintains a rigorous surgery and clinic schedule. Up at 5:30 a.m., to work by 7:00 a.m. for meetings, in the operating room for four surgeries on average, all interspersed with answering emails and dealing with various patient issues–this is a typical “surgery day” for Pockaj.

On alternate days, she makes rounds on her hospital patients and sees patients in clinic. Pockaj say that her dual roles as surgeon and clinician give her access to a larger segment of care of a patient. In her opinion, the surgeon’s role is not only to solve a specific surgical problem, but also to “orchestrate the optimal care for the patient,” with an understanding of the larger picture of a patient’s medical problems.

Pockaj’s vision of optimal medical care for her patients is also reflected in her involvement in basic research in melanoma and breast cancer. Amid her hectic schedule at the hospital and clinic, Pockaj works with researchers at Mayo Clinic and other Arizona institutes to improve the diagnosis and treatment of these deadly diseases.

Despite the pressures in her daily life, Pockaj manages to retain a fair degree of normalcy: When she returns home from work, she eats dinner with her husband and plays with her three-year-old daughter who “refuses to go to bed almost every night.” Pockaj attributes a large measure of her success in juggling her multiple roles to having “a great husband that is willing to stay home to take care of [their daughter].”

Another key element in her success could lie in her having what is referred to in the medical community as a “surgical personality.” Pockaj is very focused and decisive: Once a decision is made, she believes in efficiently moving forward to solve the problem at hand.

This forge-ahead attitude has propelled her to the head of surgical oncology at Mayo Clinic in Scottsdale and won her a 2002 McMillan Scholarship for Leadership Development from the Mayo Clinic Foundation.

Pockaj’s multi-pronged approach to patient care has also gained her admiration and respect during the nine years that she has been at Mayo.

“Dr. Pockaj brings remarkable energy, enthusiasm, and commitment to the care of her patients,” says Miller. “She extended her training in one of the foremost cancer immunology laboratories at the NIH, and constantly seeks ways to apply this experience to improve the treatment of her patients.”

Pockaj’s vision of patient care involves tackling a medical problem from multiple angles, an approach she picked up at Vanderbilt University Medical School, where she received her medical training.

While in medical school, Pockaj found herself moving in an unanticipated direction.

“I never thought that I would do surgery…ever,” she says.

That changed during her surgery rotation, when she was encouraged in the idea that the surgeon’s role was to be an “internist that can also operate” rather than as a specialist in a particular technique.

Following her medical training and residency, Pockaj took a fellowship in immunotherapy and surgical oncology at the National Cancer Institute at NIH Working at the NIH, which houses some of the top researchers in the world, was an exciting experience and “solidified” in her a resolve to pursue basic research into cancer as well as clinical and surgical work in that area.

 

Melanoma: A Growing Killer

Pockaj’s main research focus is in melanoma. This cancer originates in skin cells that produce a brown pigment called melanin and is generally marked by a change in a pre-existing mole or the appearance of a new mole on previously clear skin. There are predicted to be 55,100 new cases of this skin cancer diagnosed in the United States in 2004, placing it in the top seven most prevalent cancers diagnosed. While the incidence of most cancer types is either decreasing or holding steady, the number of cases of this potentially lethal disease is on the rise.

Melanoma is one of the few cancers in which progress has been shown, in certain cases, to be altered by boosting a patient’s immune system. This has led researchers to focus on increasing patient immune response as a potential therapy.

There are two major components to a person’s immune system. One is the B lymphocyte (B-cell) and the other is the T-lymphocyte (T-cell). When a person’s immune system is boosted by a vaccine, it is the T-cell that recognizes the foreign substance (antigen) and produces an immune response. The key component of the immune response is a cytotoxic T-cell which recognizes the foreign substance resulting in tumor cell death. These so-called “killer cells” get “help” in attacking the tumor cells from helper T-cells.

One of the things that the cytotoxic T-cell needs from the helper T-cell is a protein called interleukin-2. This protein is made by the helper T-cell and then deposited outside of the cell. There it can bind to the surface of the cytotoxic T-cell, stimulating its growth and function.

How best to harness a patient’s own immune system is still under investigation. The prospect is further complicated by the fact that most patients with cancer have some degree of immunosuppression. Pockaj has explored the immune competence of patients with breast cancer in her recent publication in the Annals of Surgical Oncology and found a significant degree of immunosuppression even in early stage breast cancer patients.

One option that exists currently is to magnify the adaptive immune response while at the same time overcoming the immunosuppression, by treating metastatic melanoma patients with a high dose of interleukin-2. There are several caveats to this approach: Only about 15 percent of patients respond to this type of therapy, and the interleukin-2 is toxic, producing harsh side effects. Bittner, Zenhausern, and Pockaj have proposed genetic profiling as a means of identifying patients who will be most responsive to this therapy, limiting unnecessary usage of the drug.

The proposal outlines Pockaj’s role in administering interleukin-2 and collecting tissue samples in a clinical trial. The mRNA, which can be thought of as gene copies, will be removed from this tissue and then bound to a gene array chip using a process and automation developed by Zenhausern at ASU.

This gene array has thousands of genes fixed onto its surface. The mRNA copy of a gene will bind to the specific gene sequence on the chip that it was made from, generating a color signal. A brighter signal will indicate that more mRNA is bound (more copies) and that there is higher expression of that particular gene in a given tissue sample.

Following analysis by Bittner’s group at TGen, a profile of the amount of each gene expressed in patients that respond to interleukin-2 will be generated and compared to the profile of a patient that fails to respond. The increased/decreased expression of a certain gene or combination of genes between the two types of patient will generate a characteristic signature that physicians can look for in deciding the best treatment option for future patients.

This approach could be applied to an array of chemotherapy drugs as well. Such a proposal will be submitted by TGen and Mayo Clinic for funding on June 1.

Pockaj believes that this “molecular targeting of drugs” is the way of the future, allowing the clinician to “tailor therapy for individual patients.”

The advent of TGen in Arizona, she believes, adds an extra dimension that will bring Mayo Clinic in Scottsdale to world-class status in its ability to recruit top researchers and clinicians.

“I couldn’t have picked a better place to live or to practice medicine than Arizona and Mayo Clinic in Scottsdale.”