Triple-negative breast cancer (TNBC) is one of the most aggressive types of breast cancer and is very hard to treat. It grows quickly,spreads early,and doesn’t have the hormone receptors that many other breast cancers do,meaning targeted drugs don’t work well. Some patients respond to treatment at first, but the cancer frequently enough comes back and is harder to treat the second time.
New research in Breast Cancer research shows a possible new way to fight this resistance.Scientists at MUSC Hollings Cancer Center created an experimental antibody to stop TNBC cells from using several ways to survive. In early tests, the antibody slowed tumor growth, reduced cancer spread to the lungs, and helped immune cells that usually attack cancer work better. The treatment also killed cancer cells that had stopped responding to chemotherapy.
Targeting a Key Cancer Enabler
The study focused on a protein called secreted frizzled-related protein 2 (SFRP2).This protein helps tumors grow by creating new blood vessels, preventing cancer cells from dying, and weakening immune cells that could kill the cancer.
This research builds on almost 20 years of work lead by Nancy Klauber-DeMore, M.D., a breast surgical oncologist who co-leads the Developmental cancer Therapeutics Research Program at Hollings. The project involved a team from MUSC’s Surgery, Biochemistry and Molecular Biology, and Pathology and Laboratory Medicine departments.
“My lab first found that SFRP2 plays a role in breast cancer in 2008,” Klauber-DeMore said. “As then, we’ve learned how it effectively works in breast cancer growth, spread, and immune exhaustion, and we’ve developed an antibody to block SFRP2.”
The research team, including MUSC surgical resident Lillian Hsu, M.D., and former resident Julie Siegel, M.D., tested a humanized monoclonal antibody. This antibody is designed to attach to SFRP2 and block its effects on cancer.
Reprogramming the Immune System Around the Tumor
To see if SFRP2 was a good target in TNBC, the researchers analyzed human tumor samples. They found SFRP2 not only in cancer cells but also in nearby immune cells, like tumor-infiltrating lymphocytes and macrophages.
“This is the first time anyone has shown that SFRP2 is found on tumor-associated macrophages,” Klauber-DeMore said. “This finding gives us a new way to understand and possibly change the immune habitat around the tumor.”
Macrophages generally fall into