Researchers discover unique metabolic vulnerabilities of subsets of triple-negative breast cancer

(Boston)—Researchers have identified a metabolic enzyme and pathway in some triple-negative breast cancer (TNBC) patients, which they hope could serve as a biomarker to select patients to receive targeted therapy.

Triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer, disproportionally affecting young Black women. The disease metastasizes quickly with 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. 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,”

explains corresponding author Hui Feng, MD, PhD, associate professor of pharmacology and medicine at Boston University School of Medicine.

Researchers in the Feng lab analyzed human patient TNBC samples, human cell lines, including those injected into animals to define the contribution of DLST to TNBC pathogenesis. Comprehensive biochemical and molecular assays were also utilized to understand the metabolic and molecular properties of TNBC 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.

These finding appear online in the journal Communications Biology.

Funding was provided by Alex’s Lemonade Stand Foundation, GR-000000165. J.A. and A.L.: Boston University, Undergraduate Research Opportunity Award. J.A. and A.K.: Alex’s Lemonade Stand Foundation, Pediatric Oncology Student Training Award. M.C.S: NIH, P01 CA104838 and R35 CA197602. H.F.: NIH, CA134743 and CA215059; Boston University, 1UL1TR001430 and Ralph Edwards Career Development Professorship; Leukemia Research Foundation, Young Investigator Award; the American Cancer Society, RSG-17-204-01-TBG; and St. Baldrick Foundation, Career Development Scholar Award.