Scientists at Cancer Research UK’s London Research Institute (LRI) and the Technical University of Denmark have developed an RNAi-based approach to determine paclitaxel response. Focusing on estrogen-receptor (ER)/progesterone-receptor (PR)/human epidermal growth factor receptor 2 (HER2; ERBB2)-negative (triple-negative) disease, they sequentially deleted 829 genes involved in cells’ response to the chemotherapy to see which missing or faulty genes would prevent the drug from working.
Their results identified six genes which, if faulty, impacted on the effectiveness of the drug in cancer cells in vitro. The team then confirmed that the same six genes in patients’ breast cancer cells could be used to predict which individuals would derive the most benefit from paclitaxel.
“Our research shows it is now possible to rapidly pinpoint genes that prevent cancer cells from being destroyed by anticancer drugs and use these same genes to predict which patients will benefit from specific types of treatment,” states Charles Swanton, M.D., head of translational cancer therapeutics at the LRI. “Now the challenge is to apply these methods to other drugs in cancer medicine and to help identify new drugs within clinical trials that might benefit patients who are predicted to be unresponsive to treatment.”
Details appear in The Lancet Oncology in a paper titled “Assessment of an RNA interference screen-derived mitotic and ceramide pathway metagene as a predictor of response to neoadjuvant paclitaxel for primary triple-negative breast cancer: a retrospective analysis of five clinical trials.”