Arthritis Drug Could Give Chemotherapy More Punch Against Triple-Negative Breast Cancer

Arthritis Drug Could Give Chemotherapy More Punch Against Triple-Negative Breast Cancer
Blocking the abnormal synthesis of DNA building blocks could restore sensitivity to a chemotherapy used to treat triple-negative breast cancer, according to a study. Researchers discovered that combining the chemotherapy Adriamycin (doxorubicin) with an inhibitor of nucleotide synthesis known as leflunomide led to significant tumor regression in mice -- an outcome that didn't occur when either drug was used alone. The U.S. Food and Drug Administration has approved leflunomide to treat rheumatoid arthritis, but not cancer. The study, "Adaptive Reprogramming of De Novo Pyrimidine Synthesis Is a Metabolic Vulnerability in Triple-Negative Breast Cancer," was published in Cancer Discovery. Unlike breast cancer subtypes driven by estrogen, progesterone, or the tumor-promoting gene HER2, triple-negative breast cancers (TNBC) lack targeted therapies. Doctors use standard-of-care chemotherapy as a first line of treatment against them. However, only 30 percent of TNBC patients achieve a complete response -- the elimination of all cancer -- after chemotherapy. And most patients with residual disease experience high rates of metastatic recurrence, a development associated with poor long-term prognosis. "Given the complete lack of any targeted therapies specific to triple-negative breast cancer, we started thinking about how we could find other vulnerabilities in tumor cells," corresponding author Alex Toker, PhD, said in a
Subscribe or to access all post and page content.