Study Identifies Triple-Negative Breast Cancer Survival Pathway
Breast cancer remains the leading cause of cancer-related deaths among women worldwide despite advances in screening, diagnosis, and treatment.
The inter-patient heterogeneity of breast cancer has long been recognized, and molecular genetic approaches have revealed distinct subgroups that are associated with different overall patient outcomes. Among these subgroups, triple-negative breast cancer (TNBC), which is defined by the lack of estrogen receptor (ER), progesterone receptor (PR), and Her2/neu receptor expression has the poorest prognosis and accounts for approximately 10% of all breast cancer cases.
Hormone therapy for breast cancer blocks cancer cells from interacting with hormones such as estrogen and progesterone, which fuel the cancer cells to grow and spread. However, triple-negative breast cancer cells lack the receptors needed to bind to these hormones and growth factors. Without such receptors, typical therapy does not work, contributing to poor survival rates for women with this subtype of breast cancer.
Now, researchers at the Cleveland Clinic have identified survival pathway in cancer stem cells that may serve as a potential target for new triple-negative breast cancer therapies. At the center of this pathway is the protein connexin 26 (Cx26), which was previously thought to curb tumor growth but may actually drive tumor progression by aiding communication between cells.
“Triple-negative breast cancer is resistant to treatment and has a high recurrence rate,” Ofer Reizes, co-author of the study said. “This aggressive subtype accounts for about 15-20 percent of breast cancers. Our findings are at an early stage but we are hopeful that targeting these cancer stem cells will lead to new treatments to allow women to be treated successfully and improve their outcomes.”
In the course of their study, the researchers studied the connexin 26 (Cx26) proteins. They compared healthy breast tissue to triple-negative breast cancer tissue and found that Cx26 is the most highly expressed connexin in diseased tissue vs. normal breast tissue. They also observed that Cx26 levels are higher in cancer stem cells than non-cancer stem cells and that the protein is expressed inside the cell rather than on the cell surface. The researchers also found that Cx26 is linked to two other proteins known to independently promote tumor maintenance and growth.
“Additional research is needed, but this discovery suggests that inhibiting Cx26 and the related pathway may be a promising new strategy for stopping or preventing triple-negative breast cancer stem cells from self-renewing and spreading,” co-author, Justin Lathia said. “It may also offer a target for diagnostic testing that helps clinicians predict health outcomes and relapse-free survival for patients with a specific cancer type.”