Trastuzumab resistance features GRK2 activation.

We studied whole tumor gene expression in humans with pathologic complete response (pCR) or residual disease (RD) following treatment for HER2+ breast cancer to discover gene expression changes associated with, resulting from or causing resistance to treatment with the HER2-targeted treatment trastuzumab (Herceptin). We identified activation of GRK2 in humans whose tumors display resistance to treatment with trastuzumab. Studying whole transcription in HER2+ breast cancer cells engineered to develop trastuzumab-resistance in vitro validated this phenomena. GRK2 activation likely supports resistance to trastuzumab in humans with HER2+ breast cancer.