Trastuzumab-Resistant HER2 Breast Cancer Cells Retain Sensitivity to Poly (ADP-Ribose) Polymerase (PARP) Inhibition.

HER2-targeted therapies, such as trastuzumab, have increased the survival rates of HER2 breast cancer patients. However, despite these therapies, many tumors eventually develop resistance to these therapies. Our lab previously reported an unexpected sensitivity of HER2 breast cancer cells to poly (ADP-ribose) polymerase inhibitors (PARPi), agents that target homologous recombination (HR)-deficient tumors, independent of a DNA repair deficiency.

Let-7 Status Is Crucial for PARP1 Expression in HER2-Overexpressing Breast Tumors.

HER2 breast tumors have been shown to express elevated levels of PARP1 protein. Yet, the mechanism by which PARP1 is upregulated in HER2 breast cancer is unknown. Here, knockdown of HER2 (ERBB2) in HER2 breast cancer cells resulted in a reduction in PARP1 protein.