UVM Scientist Wins Grant To Tackle Aggressive Forms Of Breast Cancer

Dec 5, 2016

A University of Vermont scientist recently won a $450,000 grant to continue his research that could one day lead to a new approach to treating a rare, more aggressive form of breast cancer.

The rate of women dying from breast cancer has gone down by about 2 percent over the last decade. But for about 15 percent of breast cancer cases, there isn't a targeted treatment available.

These are cases of what's known as triple negative breast cancer, which tends to be more aggressive and is associated with poorer prognosis. The main option for women with this kind of cancer is a general chemotherapy, which kills healthy cells along with cancerous ones.  

But in the course of studying basic cell division in the body, UVM's Jason Stumpff began investigating a specific protein. And it turns out this molecule could hold a key to how these aggressive tumor cells associated with triple negative breast cancer proliferate.

Stumpff has been studying how human body cells divide and reproduce for about two decades.

He wasn't focused specifically on breast cancer until one day "a serendipitous observation" led him to realize that certain breast cancer tumor cells "require one of the proteins we've been working on in my lab for division."

Remember, cell division means growth. The kicker to this discovery is that this protein that the tumor cells rely on does not seem to be crucial for normal body cells to reproduce. That means that targeting this protein could cripple the tumor cells without hurting health body cells. 

That's the hypothesis Stumpff's lab will be testing.

The molecule Stumpff is studying is a kind of kinesin, which is a protein involved in the process of mitosis.

If you remember back to high school biology, the process of mitosis is where the human cell divides,  creating two daughter cells with the same DNA.

The cell division process is part of how ordinary growth occurs in our blood cells and organs — and how the body repairs tissue. In human bodies, nearly two trillion cells divide every day.

Cancer occurs when cell reproduction gets out of control and tumor cells multiply without the body stopping the growth.

Tackling the more aggressive breast cancers

With about 85 percent of breast cancers, there are existing treatments that specifically target certain receptors on the tumors. The drugs work by inhibiting the receptor, keeping the tumor from communicating and therefore stopping it from multiplying. 

But there are other forms of breast cancer that don't rely on any of these three common receptors to multiply: the group called triple negative breast cancer.

"The problem with triple negative breast cancers is they don't have any targets," says Stumpff. "So at this point there are no known molecular targets for triple negative breast cancer, and the only way to treat those types of tumors is to give patients what we call 'cytotoxic agents.'"

That's a type of chemotherapy that basically blasts all the cells multiplying in that area — both healthy and tumor cells.

"So when you get into diagnosis of triple negative, that's pretty bad," says Carol Vallett, a breast cancer survivor who is serving as a patient advocate to advise Stumpff's research.

"There's chemotherapies, there's treatments, but there isn't one drug or protocol that will stop and cure that cancer. That's why triple negative breast cancer is considered a very important problem," Vallett says.  

This is an image of a dividing cell from Jason Stumpff's lab. The blue is the DNA. The red lines are microtubules, which help move the chromosomes into place before the cell splits into two.
Credit Cindy Fonseca / UVM

The $450,000 grant Stumpff recently was awarded from Susan G. Komen requires that he seek the input of breast cancer patients or family members to help guide the research in a meaningful direction.

Vallett and Marion Thurnauer, a breast cancer survivor based in Colorado, will meet with Stumpff quarterly to review the progress of the research.

Patients advising lab scientists

Thurnauer was diagnosed with breast cancer 27 years ago, before many of today's treatments existed. She underwent a mastectomy and had some lymph nodes removed. The procedures were successful in removing the cancer, but she later developed a swelling in her arms called lymphedema, which can occur in the arms or legs after the removal of her lymph nodes.

Thurnauer says part of the role in advising scientists is helping them understand the impact of treatment.

She says if the science research concluded that, "'Well, we could do this to a patient, and we would perhaps get this good result.' If you're a patient and not a scientist [you're] sitting there and thinking, 'What are the side effects?' 'Well, how would this affect me? Would I really want this treatment?'"

After surviving breast cancer, Vallett also sought out all kinds of ways to give back to the patient and medical community that had supported her.  

She reviews science research grant applications for the federal government and she has volunteered for multiple clinical trials — that's research or drug trials that involve patients. 

"It's not immediate. It's not like the answer will be ... 'Next year, on the market.' That doesn't happen. It's a long process." — Carol Vallett, patient advocate

"I always said 'Yes,' because I'm a strong believer in research. This is how we advance treatment, we advance science, we advance benefits to patients of all sorts," says Vallett. "But what I came to realize after attending the breast cancer conference in 2007 — it's not just clinical research that we see, but there's so much lab research that happens first."

In fact, it takes years and years of lab research to simply understand all the cellular processes involved before even considering making a treatment drug.

The long road toward developing treatments

Puck Ohi knows this firsthand. He researches cell and developmental biology at the Vanderbilt University School of Medicine.

Ohi says strategies that work in the lab don't always translate into a successful drug development, at least not right away. He gives the example of a molecule called Eg5, that some tumor cells rely on to divide. When scientists blocked that molecule in the lab, it inhibited tumor growth. 

But when it comes to human bodies, it's not so simple. Ohi says multiple pharmaceutical companies have been running clinical trials testing a drug that targets the Eg5 molecule.

"In every case, these Eg5 inhibitors have failed," says Ohi. "So now we're in damage control mode to figure out why these inhibitors didn't work, and if there's a way to make them better."

Ohi says his lab has several hypotheses about how cancer cells can adapt to presence of these inhibitors, how the tumors cells are proliferating even when the Eg5 is blocked. 

Ohi has also worked with UVM's Jason Stumpff studying the role of the kinesin molecule Stumpff is researching. He says there's real potential in targeting this kinesin.

Ohi says he believes Stumpff's research will determine if this molecule would be a good candidate to develop a drug.

Beyond tumors: Going after metastasis

There's another interesting aspect to this protein, says Alan Howe, a pharmacology researcher at UVM who is collaborating with Stumpff. Howe studies cell migration, which is when tumor cells move beyond the tissue they originated in and spread to other parts of the body. This is how cancer metastasizes and often becomes deadly.

The kinesin Stumpff studies is mainly involved in helping cell division, but Howe says some studies have observed that sometimes the protein may occasionally play another role as well.

"There's a very small portion of [the protein] that moonlights in cells that are not actively dividing at all," says Howe. He says there's some evidence that the protein "seems very dynamic in the very front and the very back of cells as they're migrating — it's pretty crazy."

That dynamism could mean the protein is involved in cell migration, which makes it an even more exciting potential target. It introduces the idea that attacking the protein could fight triple negative breast cancer tumors and metastasis in one blow.

Still, it's early days in the research. And along the way, Stumpff will have the support and mentorships from patient advocates.

"It's our role also to keep asking questions of him and his mentoring group: 'So, how will this make a difference? When might we see something?'" says Vallett.

"And a lot of the bench-to-bedside work, it's not immediate," she says. "It's not like the answer will be, "Oh, so next year, on the market.' That doesn’t happen. It's a long process. And even if the goals and success that is initially laid out don't happen, there's always good learning that comes out of this."

This report comes from the New England News Collaborative: Eight public media companies coming together to tell the story of a changing region, with support from the Corporation for Public Broadcasting.