Predicting response to platinum chemotherapy via marker of DNA damage

Scientists have uncovered a marker of DNA damage that could predict who will respond to platinum-based chemotherapy drugs like cisplatin or carboplatin. These drugs are widely used for ovarian cancer, but as with most cancer drugs, it can be difficult to predict who will respond to therapy. A team of researchers from the Dana-Farber Cancer Institute found that this marker, telomeric allelic imbalance or tAI, could predict sensitivity to therapy in patients with triple-negative breast cancer. The results are published in Cancer Discovery, a journal of the American Association for Cancer Research. "We currently do not have any targeted therapies for patients with triple-negative breast cancer, so if these laboratory findings are confirmed and an assay is created to predict sensitivity to drugs that target defective DNA repair, it would be a major step forward," said lead pathologist Andrea Richardson, M.D., Ph.D., assistant professor of medicine at Dana-Farber Cancer Institute. Scientists have long known that DNA repair status is a predictor of sensitivity to therapy and thus prognosis. However, measurements of DNA repair status have been slow to arrive. Richardson and colleagues looked for genomic signatures in cell lines and tumors and correlated them to platinum sensitivity. In patients with triple-negative breast cancer, they found that a high level of subchromosomal regions with allelic imbalance extended to the telomere predicted response to cisplatin treatment. The same was true for serous ovarian cancer. Importantly for patients with triple-negative breast cancer, researchers found an inverse relationship between the level of tAI and BRCA1 expression.