Treating triple negative breast cancer cells with erlotinib plus a select antioxidant overcomes drug resistance by targeting cancer cell heterogeneity

• DOI: 10.1038/srep44125
• Publication Date: 2017-03-10T10:19:57Z
• Authors: Bin Bao; Cristina Mitrea; Priyanga Wijesinghe; Luca Marchetti; Emily Girsch; Rebecca L. Farr; Julie L Boerner; Ramzi Mohammad; Greg Dyson; Stanley R. Terlecky; Aliccia Bollig-Fi...
• Keywords: Triple-negative breast cancer; EGFR Inhibitors

Abstract Among breast cancer patients, those diagnosed with the triple-negative (TNBC) subtype have worst prog-nosis. TNBC does not express estrogen receptor-alpha, progesterone receptor, or HER2 oncogene; therefore, lacks targets for molecularly-guided therapies. The concept that EGFR oncogene inhibitor drugs could be used as targeted treatment against has been put forth based on estimates 30–60% of high levels EGFR. However, results from clinical trials testing inhibitors, alone in combination cytotoxic chemotherapy, did improve patient outcomes. Results herein offer an explanation to why inhibitors failed patients and support how combining a select antioxidant EGFR-specific small molecule kinase (SMKI) effective, novel therapeutic strategy. Treatment CAT-SKL—a re-engineered protein form enzyme catalase—inhibited stem-like cells (CSCs), SMKI erlotinib inhibited non-CSCs. Thus, CAT-SKL both CSCs bulk cultures EGFR-expressing TNBC-derived cells. We also report evidence mechanism inhibition may depend antioxidant-induced downregulation short alternative mRNA splicing variant methyl-CpG binding domain 2 gene, isoform MBD2c.