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On the front line
Researchers discovering new treatments to fight cancer


April 2013

It’s a milestone year for the Medical College of Wisconsin — the 100th anniversary of the founding of its predecessor, the Marquette University School of Medicine. But every year is big for researchers at MCW (as it became known in 1970). In 2012, it received more than $95 million in funding from the National Institutes of Health and conducted over 2,000 studies — big numbers that could yield big changes in cancer treatment.

Progress in the Melanoma Fight

Science is unlocking the mystery of how melanoma develops, and not a moment too soon, with cases steadily increasing during the past 30 years.

"One of the big breakthroughs is the knowledge that there are some very specific mutations, what we call driver mutations, in the skin cells that actually cause the disease," says Dr. Stuart Wong, medical oncologist at Froedtert & The Medical College of Wisconsin. "This has allowed researchers to develop drugs that block the pathways (of melanoma development)."

In 2011, a drug called vemurafenib was fast-tracked for approval because it showed dramatic results in what was supposed to be a three-year clinical trial. It saved the life of one of Wong’s patients.

"Literally, he went from his deathbed to walking out of the hospital in 10 days," recalls Wong. "You could see his lab studies dropping down before our eyes, just seeing his symptoms melt away."

Now, Wong and an MCW research team hope to go even further. They are part of an international effort studying whether a combination of drugs could block multiple pathways of driver mutations in Stage IIIc and Stage IV patients. "It’s a one-two punch," says Wong.

Estimates are that more than 76,000 Americans (including 1,250 people in Wisconsin) will be diagnosed with melanoma in 2013. It represents just 5 percent of all skin cancer cases, but the vast majority of skin cancer deaths (about 9,400 nationally per year) because it spreads to other parts of the body.

"There are a lot of global efforts going into melanoma," notes Wong.

Last fall, researchers in Boston announced they had discovered a way to reverse tumor cell growth by potentially repairing a biochemical defect on the DNA structure. Wong calls it "an interesting and important study that tells an overall study of how what happens in the laboratory can be translated into the clinic."

Tumor cells are very smart, continuing to mutate and create new pathways so they can survive, Wong says. "It’s a continual process for us, to be smarter than the tumor cells and think of more innovative ways to get these tumors under control."


The 10 Percent Solution

An important part of the body’s defense system is the cells known as natural killers. They make up less than 10 percent of the circulating white blood cells but can fight viruses, parasites and even cancer.

Patients with high-risk solid-tumor cancers — which cause six in 10 pediatric cancer deaths — may soon be able to parlay that 10 percent into better outcomes. Immune system treatment capitalizing on NK cells could be approved for use just months from now.

A gentle chemotherapy regimen is the first step, according to Dr. Monica Thakar, an assistant professor of pediatrics whose research team developed the new approach. The next step is a bone marrow transplant from a family member who needs to be only a half match; a week later, the patient receives an infusion of NK cells from the same donor.

"While we have made tremendous strides in curing children with leukemias and lymphomas over the past 30 years, we have not been so successful with many types of solid tumors," Thakar says.


Keeping the T Cells Working

T cells are the body’s bomb-sniffing dogs, searching through the bloodstream for tumor cells and killing them. Problem is, tumors can turn off the T cells, rendering them as useless as a security dog without a sense of smell.

Immune therapy seeks to make sure T cells are activated in sufficient numbers to kill tumor cells, according to Jill Gershan, an assistant professor of pediatrics, who is leading a study on multiple myeloma treatments.

When patients are given very high doses of chemotherapy and/or radiation, those therapies destroy important "progenitor" cells (that give rise to all types of blood cells) as well as most of the white blood cells in the body. Little wonder that patients with this blood cancer have an average survival prognosis of only three to five years.

Gershan’s study is looking at a combination of two immune-based strategies. First, progenitor cells would be harvested from the patient. Later, those cells would be returned to the patient just before introducing an antibody to block a harmful protein on the surface of myeloma tumor cells. "This appears to ‘make space’ so that the T cells can expand and become fully activated," says Gershan, calling the study results thus far "encouraging."


This story ran in the April 2013 issue of: