Targeting And‐1 to overcome radiation resistance in colorectal cancer

Abstract

Abstract Colorectal cancer (CRC) is a leading cause of cancer‐related death worldwide. Although overall outcomes have improved in recent decades, metastatic disease is associated with a particularly poor prognosis, underscoring a need to both identify new therapeutic modalities as well as actionable mechanisms of resistance to the current standard of care treatments. Radiation is an important part of treatment for many rectal cancer patients and is under extensive investigation in CRC. A recent study by Zhao and colleagues published in Clinical and Translational Medicine has identified novel insight into radiation resistance in CRC, as well as a potential means of enhancing therapeutic responses to radiation. The authors determined that O‐GlcNAcylation of the DNA repair protein And‐1 is an obligate step in And‐1‐mediated double‐strand break homologous recombination (HR). They also show that this phenomenon drives radiation resistance in vitro and can be overcome by repurposing the selective estrogen receptor modulator (SERM) bazedoxifene acetate as an And‐1/HR inhibitor.

Keywords

• colorectal cancer
• homologous recombination
• radiation