A new study led by UK Markey Cancer researchers and published in the Journal of Cell Science establishes a novel link between cell polarity and cancer-associated inflammation.

Proposed clinical trial could change the game for triple-negative breast cancer

This is the first post in a two-part series about UK Markey Cancer Center researchers’ efforts to improve treatment for triple-negative breast cancer, a deadly form of the disease. Check out Part Two here.

UK Markey Cancer Center Oncologist Dr. Edward Romond spent his career at UK treating and studying breast cancer, even leading major Phase 3 clinical trials on the breast cancer drug trastuzumab in the early 2000s. Commonly known as Herceptin, this drug became a standard of care for patients with HER2-positive breast cancer.

Though he retired from practice last year, Romond continues to work part-time with the research team at Markey, this time pushing toward a cure for a different, more deadly, type of breast cancer.

“Breast cancer, we now recognize, is at least five different diseases that are completely different from each other,” Romond said. “And the hardest nut to crack is this one called triple-negative breast cancer.”

Treating triple-negative breast cancer

Triple-negative breast cancer is a moniker given to a particularly aggressive group of breast cancers that often affect younger women. Unlike the receptor-positive types of breast cancer, which have biomarkers that tell oncologists which treatment the patient should respond to, triple negative breast cancers have no definitive biomarkers. If the patient does not respond well to the current standard of care, it’s up to the oncologist to make an educated guess about which chemotherapy will do the job.

The good news is that triple-negative breast cancers do generally respond well to chemotherapy. However, because triple-negative breast cancers are not the same, and every single patient responds differently to various chemotherapies, it’s difficult to predict which chemotherapy will best treat each patient’s cancer.

But the researchers at Markey are working to change that paradox. Markey’s Breast Translational Group is currently developing a proposed clinical trial that could create a major shift in the way triple-negative breast cancers are treated.

Currently, after a patient is diagnosed with triple-negative breast cancer, she usually receives chemotherapy first to try and shrink the tumor (known as neoadjuvant therapy), followed by surgery to remove as much of the mass as possible. The patients are then monitored for signs of recurrence. If a patient has residual cancer despite getting neoadjuvant chemotherapy, they are at a high risk for recurrence.

Proposed clinical trial

There are currently at least six different types of chemotherapy that can be used as a possible therapy for patients, and each one may affect each individual patient in a different way. To tailor the treatment to each distinct patient, the investigators aim to test the tumors in a set of animal model “avatars” with these different therapies to gauge the response.

Here’s how the proposed trial would work: after the patient’s biopsy, her cancerous tissue would be transferred into a mouse that is bred to grow human tumors, then subsequently into three dozen mice: her “avatars.” While the patient undergoes neoadjuvant chemotherapy and then surgery – a process that can take up to six months – the avatars will be divided into groups, with each group receiving one of the six available chemotherapies.

When the researchers see which avatar group has the best result, they’ll know which chemotherapy should work best for that patient. Knowing this would provide additional options for women who have residual cancer after neoadjuvant chemotherapy, and may reduce their risk for disease recurrence.

“It would prevent us from having to experiment with each individual patient, and end up finding that they didn’t respond to that therapy,” said Kathleen O’Connor, director of Markey’s Breast Translational Group. “If we can do this, then the oncologists will no longer have to guess.”

Disrupting the standard of care

Dr. Aju Mathew, a medical oncologist who treats triple-negative breast cancer patients at Markey, compares his team’s game-changing proposition to the way Uber has altered the use of public and personal transportation.

“We often hear about disruptive technology — Uber being one, for example,” he said. “It disrupted the current paradigm of everyone driving a car on their own or hiring a cab. This trial is our way of disrupting the current standard of care, the current technology, and the current practice of medicine, to try to change the paradigm of ‘one size fits all’ approach for triple-negative breast cancer patients.”

Though the avatar model of research isn’t new, O’Connor notes that not many researchers are using them specifically for the treatment of an individual patient. Using a trial protocol to get the tissues directly from the patient’s biopsy is a key factor in making the research work.

“The important thing is that we need to get the tumor tissue before they’ve been exposed to chemotherapy,” O’Connor said. “This is one of the things that makes our trial unique.”

With the trial design in place, the team just needs to provide ample data showing that growing a patient’s tumor in the avatar from biopsy will work. But to gather that data, they need more funding. Initial pilot funds stemming from Markey’s National Cancer Institute (NCI) designation grant have enabled the team to establish their first set of avatars with tissues taken from patients’ surgeries. But a boost in funding would help them establish the preliminary data for the trial and allow the team to then apply for major federal funding.

“We have a large group of people who have freely given their time up to this point,” O’Connor said. “But we need to have money to protect the time of the researchers doing this work, and we need enough money to get the mice in order to do this.”

Check out the video below to see Markey researchers talk about their triple-negative breast cancer research.


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