CLEVELAND, Ohio – For the past several years, researchers from the Cleveland Clinic and Case Western Reserve University School of Medicine have been collaborating on studies that could lead to new ways to fight triple-negative breast cancer.
Their latest finding: By keeping
CLEVELAND, Ohio – For the past several years, researchers from the Cleveland Clinic and Case Western Reserve University School of Medicine have been collaborating on studies that could lead to new ways to fight triple-negative breast cancer.
Their latest finding: By keeping two proteins found in human cells from interacting with each other, the rate at which the deadly breast cancer subtype spreads can be slowed down.
The team -- led by Khalid Sossey-Alaoui, research assistant professor in the department of molecular cardiology at the Clinic’s Lerner Research Institute, and William Schiemann, an associate professor in the division of General Medical Sciences-Oncology at CWRU’s medical school – documented their findings in a paper published in November in the journal Breast Cancer Research and Treatment.
Funding for the research came from the National Institutes of Health, the U.S. Department of Defense and the Case Comprehensive Cancer Center.
The focus is on two proteins. WAVE3 is found in advanced breast cancer cells, or cancer that has metastasized. And almost every cell in the body can make transforming growth factor, or TGF-β, which helps to lessen the rate of tumor growth. But when the two proteins inhabit the same space, they promote tumor aggressiveness.
“In early-stage breast cancer, [TGF] is a tumor suppressor,” Sossey-Alaoui told The Plain Dealer. “In advanced breast cancer, it becomes a tumor promoter. That’s the paradox.”
Explained Schiemann, who is co-leader of Case Comprehensive’s Breast Cancer Program, “There’s a certain stage that [TGF] starts to play for the other team. We’ve been really interested in that switch.”
Discovered in 2000, WAVE3 is a protein that keeps cell shape together. Without it, cells aren’t mobile. Cancer cells need the protein in order to migrate and invade tissue, said Sossey-Alaoui, who has studied WAVE3 for more than a decade. Take WAVE3 out of the cell, the researchers discovered while studying cancer tissue in mice and humans, and the cancer becomes less aggressive.
That knowledge is being used to develop agents that will keep the proteins from interacting with each other, thereby slowing down the rate at which triple negative breast cancer spreads. Lab studies will begin in a couple of months, followed by studies in mice. It will be a few years before human trials are conducted.
Triple-negative breast cancer accounts for about 20 percent of all breast cancers. Extremely aggressive and more likely to recur than many other types, it’s one of the most deadly. Unlike other breast cancers, for which there are drugs to target the substances -- estrogen, progesterone and HER2 -- found inside breast cells that give rise to cancer, triple-negative lacks those three receptors.
Sossey-Alaoui joined the Clinic in 2008; Shiemann arrived at CWRU in 2010. After learning about their mutual interest in triple-negative breast cancer, Case Comprehensive Director Dr. Stanton Gerson brought them together.
Previous research by the team -- continuing work that Sossey-Alaoui began at Roswell Park Cancer Institute in Buffalo, N.Y. -- identified WAVE3 as a biomarker that served as a good predictor for breast cancer metastasis and relapse, and whether or not a patient would die of the disease. Patients with triple-negative breast cancer, they found, had extremely high levels of WAVE3 in their tumors, which could help with early detection.
Moving forward, the team is working on ways to deliver therapies to breast cancer tumors that will reverse the disease. One thing that remains uncertain - if the two proteins are present in all subtypes of triple-negative breast cancer.
“A lot of us are looking at data to try to answer that question,” Schiemann said. “Not all triple-negative cancers are the same.”
Assuming that they will be able to secure enough funding to continue moving their research forward, Sossey-Alaoui said he is confident that more breakthroughs will happen -- and quickly -- over the next five years.
"The first 10 years were trying to understand what’s going on,” Sossey-Alaoui said. “We’re beyond that now."