Identification of Quinones as growth inhibitors of Trastuzumab resistant breast cancer cells

I 2013, the number of new cases of breast cancer in the US was 234, 580 and ~1.7 million worldwide. Despite the advances in early detection and treatment of breast cancer, about 30% of patients with early stage breast cancer have recurrent disease where resistance to therapy is common and expected. HER2 is overexpressed in 20-40% of invasive breast cancer, and 12-24% of these patients develop resistance within 6 months for the widely used therapy trastuzumab. HER2 oncogenic variant HER2 16 has been shown to promote receptor dimerization, cell invasion and also trastuzumab resistance of NIH3T3 and MCF-7 tumor cells lines. We have identified several naphthoquinones that show growth inhibition of the MCF-7 HER216 cell lines with a significantly higher potency than the present clinically used tyrosine kinase inhibitor lapatinib. These compounds also inhibit auto-phosphorylation of the Y1248 and Y1068 residues of HER2 and EGFR, respectively.