Abstract P6-07-30: Identifying novel glycosylation markers in Her2+ breast cancer using MALDI mass spectrometry

Abstract

Abstract Breast cancer characterized by human epidermal growth factor receptor 2 (HER2) overexpression represents approximately 25-30% of all breast cancer cases. Many patients acquire resistance to current chemotherapies, leading to a more aggressive disease state with severe clinical outcomes. Lapatinib, a first generation tyrosine kinase inhibitor of HER2 and EGFR (epidermal growth factor receptor), is commonly used to treat HER2+ breast cancer. Resistance to lapatinib is steadily increasing among HER2+ patients, highlighting the need for therapy development. Identifying markers that predict treatment response or potential drug targets could enhance treatment efficacy and patient survival. To investigate this, we have used MALDI mass spectrometry to identify N-linked glycans specific to human breast cancer cell lines with known resistance and sensitivity to lapatinib treatment, JIMT-1 (resistant) HER2+ and BT474 (sensitive) HER2+. After different lapatinib dose and time course experiments, N-linked glycans were isolated and comparatively profiled by high resolution MALDI mass spectrometry. Differences in the levels of fucosylation and sialylation of glycans from sensitive and resistant cell lines, before and after treatment, were evaluated. In addition, mouse xenograft tumor tissues derived from the same cell lines treated with and without lapatinib were processed for on-tissue imaging of N-glycans using a MALDI imaging mass spectrometry approach. Tissues from HER2+ human breast tumors were also imaged with the same MALDI imaging approach. Cumulatively, these preliminary studies have identified novel glycosylation patterns associated with lapatinib treatment sensitivity and resistance. Citation Format: Scott DA, Angel P, Xu H, Drake R, Yeh E. Identifying novel glycosylation markers in Her2+ breast cancer using MALDI mass spectrometry [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-07-30.