Mason Research Center Attacks Breast Cancer in Three Ongoing Trials
By Michele McDonald
The Center for Applied Proteomics and Molecular Medicine (CAPMM) has three ongoing research projects that span the full scope of breast cancer’s impact on patients, including one in which a malarial drug is showing promise in stopping breast cancer before it starts.
“The bold long-term goal is a short-term oral treatment that prevents breast cancer by killing the precursor cells that initiate breast cancer,” says Lance Liotta, codirector of Mason’s , “and it’s looking hopeful.”
Chloroquine for Every Woman?
The Preventing Invasive Neoplasia with Chloroquine (PINC) trial targets ductal carcinoma in situ, or DCIS, the most common type of pre-invasive breast cancer. Chloroquine is a drug given to prevent or treat malaria, which shows promise in the early phase of the PINC trial.
In the PINC trial, DCIS is the focus. DCIS shows up as white spots in the MRI of a breast. Those white spots are calcifications that may mark the milk ducts where DCIS cells are growing, says Virginia Espina, an assistant research professor at CAPMM. Not all DCIS becomes cancer, but all breast cancer goes through the DCIS stage, she says.
If the patient is diagnosed with DCIS after a biopsy, she can enter the trial, says Espina, adding that the study doesn’t interfere with standard medical treatment. Mason researchers are working with surgeon Kirsten Edmiston, MD, at Inova Fairfax Hospital who recruits patients and clinically directs the trial.
While patients are waiting between their diagnosis and their surgery, they take chloroquine once a week for four weeks, Espina says.
A significant reduction in the lesion’s size is the sought-after outcome, says Espina, who can be seen in this video describing individual differences in cancer. The widely prescribed malaria drug chloroquine has few side effects—a rare rash is one, Espina says. There could come a day when chloroquine is taken by women worldwide to prevent breast cancer.
“We can imagine that in the future every woman will take chloroquine once a year,” Espina says. “Chloroquine kills off the premalignant cells that are starting to accumulate. You would do this periodically as a new type of chemo prevention.”
Chloroquine works by stopping autophagy, which is used by cells to survive under stress. “When cells realize they don’t have enough nutrients, they eat themselves,” Espina says. “It’s a way to make energy when you don’t have enough food.”
And that’s the spot the DCIS cells are in as they pile up in the milk duct. They’re not getting enough oxygen and food and are squashed together.
“It’s like being in an elevator,” Espina says. “You’re next to people but not necessarily next to people you know or like. It’s the same way for these tumor cells or premalignant cells. They’re next to a cell, but they’re not anchored anywhere, and cells like to be anchored and have a home.
“For all these reasons, they’re under stress. When a cell is under stress, it’s a life-and-death struggle. They’re not just going to die. They’re going to do what they can to survive. That’s when they use autophagy to stay alive.”
Chemotherapy, a common treatment for cancer, can rev up autophagy, Espina says. “A doctor selects a treatment to try to kill the cell, but the cell is trying to survive; it’s trying to do what it’s programmed to do. We have to find a way to defeat this cellular process.”
Chloroquine works like Pepto-Bismol; it alters the cell’s digestive process and therefore autophagy. “But the chloroquine doesn’t kill the normal cells because the normal cells aren’t dependent on autophagy to survive,” Espina says.
The Department of Defense Breast Cancer Research Project is funding the majority of the $2.1 million, three-year PINC grant, which started two years ago.
Individualized Treatment for Metastatic Breast Cancer
In the second CAPMM study on breast cancer, researchers are developing individualized treatment for women with metastatic breast cancer. These advanced tumors have spread to other organs, such as the liver, and brain and bone and have limited response to conventional therapies. Standard chemotherapy failed the 25 women Mason has worked with to pinpoint more effective treatments, says Mariaelena Pierobon, an assistant research professor at the center.
Pierobon is using technology created by Liotta and Emanuel “Chip” Petricoin III to identify which drug targets are activated within each patient tumor. Pierobon’s team is building on the promise of personalized medicine by focusing on the molecular profile of the metastatic lesions.
“We hope that by providing physicians with detailed information on the mechanisms that are driving our patients’ tumors, we can facilitate the selection of the most appropriate treatment,” Pierobon says. “We are trying to guide that decision by using the cutting-edge molecular technologies that were created in our laboratory to select among the Food and Drug Administration (FDA)-approved drugs that might be the most promising for each patient.”
In this approach, patients don’t have to wait for new drugs to be developed. “By using drugs that are already approved, you don’t have to study toxicity. That’s a huge advantage,” Pierobon says.
The third study is the I-SPY 2 Trial in which CAPMM researcher Julia Wulfkuhle is leading molecular profiling efforts developed uniquely in the Mason laboratory for women with stage II and III breast cancer. The FDA singled out I-SPY 2 as a leading trial design for accelerated drug approval.
The Side-Out Foundation is sponsoring the ongoing CAPMM research studies on the I-SPY 2 Trial through the Foundation for the National Institutes of Health. The foundation raised $370,000 through volleyball tournaments to fund the metastatic breast cancer trial.
This article originally appeared on the university’s News site.
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