Triple-Negative Breast Cancer Biomarker A Potential Therapy Target

Boston University School of Medicine researchers have discovered a metabolic enzyme and pathway in some triple-negative breast cancer (TNBC) patients. According to researchers, the hope is that their findings can serve as a biomarker in identifying patients that could benefit from targeted therapy.

Triple-negative breast cancer is unique in the sense that it does not have any of the receptors that are typically found in breast cancer, according to the Centers for Disease Control and Prevention. For this reason, treatment options are the disease are typically limited.

“Often, patients first need to have the lump removed (a lumpectomy) or the entire breast removed (a mastectomy),” the CDC notes. “Then they have chemotherapy treatments to target any cancer cells that can’t be seen — cells remaining in the breast or that may have spread into other parts of the body. Sometimes doctors recommend chemotherapy before surgery to shrink the cancer.”

Additionally, triple-negative breast cancer is the most aggressive form of breast cancer and disproportionately impacts young Black women, creating health disparities. Over time, researchers have found that the disease metastasizes quickly and has high relapse and mortality rates.

“Our work shows that a fraction of TNBC with high expression of dihydrolipoamide S-Succinyltransferase (DLST), a metabolic enzyme, in their tumor cells depends on the TCA-cycle for survival,” corresponding author and associate professor of pharmacology and medicine at Boston University School of Medicine, Hui Feng, MD, PhD, said in a press release.

“Hence, DLST expression could serve as the biomarker to select TNBC patients to receive CPI-613, a drug currently in clinical trial for treating other cancers.”

The research team in the Feng lab analyzed human patient triple-negative breast cancer data samples and human cell lines, including those used to define the contribution of DLST to TNBC pathogenesis. Additionally, comprehensive biochemical and molecular assays were used to understand the metabolic and molecular properties of the triple-negative breast cancer cells.

“Due to current challenges in treating triple-negative breast cancer, our studies suggest that a fraction of patients with aggressive tumors can benefit from CPI-613, a drug disrupting the TCA cycle if their tumor cells have high DLST expression,” said Feng.

Researchers can develop targeted therapy that specifically attacks triple-negative breast cancer tumors by identifying potential biomarkers, improving patient outcomes. While targeted therapy does not work for all patients, it provides another option for patients who might not see the benefits of traditional treatment approaches.