Characterization of RTK Tyrosine Phosphorylation in Response to Chemotherapy Drugs in Triple Negative Breast Cancer

Abstract

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is characterized by the absence of receptors commonly found in breast cancer. Due to the lack of critical biomarkers, there are no targeted therapies for TNBC and as a result TNBC cases tend to have poorer prognosis and shorter relapse‐free survival than other types of breast cancer. One of the most well‐established therapeutic targets in breast cancers are receptor tyrosine kinases (RTKs). In TNBC, about half of the cases overexpress a subtype of RTKs called the epidermal growth factor receptor (EGFR) family. However, the outcome of EGFR‐targeted therapies in TNBC patients have been disappointing due to lack of established biomarkers that indicate sensitivity to EGFR inhibitors in patients. Previous studies have shown that studying tyrosine phosphorylation (pTyr) in signaling pathways can be quantitated to measure unique dysregulation of RTK signaling networks in patient samples. In this study, we use liquid chromatography‐mass spectrometry (LC‐MS) techniques to identify and quantify pTyr in TNBC in response to the following chemotherapy treatments: Taxol (genotoxic) and Erlotinib (EGFR inhibitor). We evaluated viability of TNBC cells in‐vitro­in response to Taxol and Erlotinib, where Erlotinib appeared to have an antagonist effect when paired with Taxol. LC‐MS results provided further evidence of the antagonist effect of Taxol and Erlotinib in the following markers: EGFR, AURKB, ITGA3, and ITGB1. These results could reveal potential biomarkers that indicate tumor sensitivity to targeted therapies in TNBC.