PaRp inhibitors, both as monotherapy and in combination with cytotoxic drugs, are currently undergoing clinical trials in several diferent cancer types. In this investigation, we compared the antiproliferative activity of two paRp/putative paRp inhibitors, i.e., olaparib and iniparib, in a panel of 14 breast cancer cell lines (seven triple-negative and seven nontriple- negative). In almost all cell lines investigated, olaparib was a more potent inhibitor of cell growth than iniparib. Inhibition by both drugs was cell line-dependent and independent of the molecular subtype status of the cells, i.e., whether cells were triple-negative or non-triple negative. although the primary target of paRp inhibitors is paRp1, no signiicant association was found between baseline levels of paRp1 activity and inhibition with either agent. similarly, no signiicant correlation was evident between sensitivity and levels of CDK1, BRCa1 or miR-182. Combined addition of olaparib and either the CDK1 inhibitor, RO-3306 or a pan heR inhibitor (neratinib, afatinib) resulted in superior growth inhibition to that obtained with olaparib alone. We conclude that olaparib, in contrast to iniparib, is a strong inhibitor of breast cancer cell growth and may have eicacy in breast cancer irrespective of its molecular subtype, i.e., whether heR2- positive, estrogen receptor (eR)-positive or triple-negative. Olaparib, in combination with a selective CDK1 inhibitor or a pan heR inhibitor, is a potential new approach for treating breast cancer.
- Breast cancer
- PARP inhibitors