N-linked Glycosylation is a Novel Target for Radiosensitization

Abstract

Tumor cell proliferation and survival are dependent upon both unique and redundant signaling cascades initiated by receptor tyrosine kinases (RTKs) in response to either growth factors or ionizing radiation. Inhibition of specific receptors (i.e., EGFR) has been shown to enhance cancer cell radiosensitivity in multiple tumor models. However, therapeutic resistance can be mediated by non-targeted receptors coexpressed by tumor cells. We hypothesized that disrupting N-linked glycosylation, a critical and highly regulated post-translational modification, would be an effective strategy to disrupt the function of multiple RTKs over-expressed by tumor cells.