Shah, FenilLogsdon, DerekMessmann, Richard A.Fehrenbacher, Jill C.Fishel, Melissa L.Kelley, Mark R.2017-10-242017-10-242017-06-08Shah, F., Logsdon, D., Messmann, R. A., Fehrenbacher, J. C., Fishel, M. L., & Kelley, M. R. (2017). Exploiting the Ref-1-APE1 node in cancer signaling and other diseases: from bench to clinic. Npj Precision Oncology, 1(1), 19. https://doi.org/10.1038/s41698-017-0023-0https://hdl.handle.net/1805/14363Reduction-oxidation factor 1-apurinic/apyrimidinic endonuclease (Ref-1/APE1) is a critical node in tumor cells, both as a redox regulator of transcription factor activation and as part of the DNA damage response. As a redox signaling protein, Ref-1/APE1 enhances the transcriptional activity of STAT3, HIF-1α, nuclear factor kappa B, and other transcription factors to promote growth, migration, and survival in tumor cells as well as inflammation and angiogenesis in the tumor microenvironment. Ref-1/APE1 is activated in a variety of cancers, including prostate, colon, pancreatic, ovarian, lung and leukemias, leading to increased aggressiveness. Transcription factors downstream of Ref-1/APE1 are key contributors to many cancers, and Ref-1/APE1 redox signaling inhibition slows growth and progression in a number of tumor types. Ref-1/APE1 inhibition is also highly effective when paired with other drugs, including standard-of-care therapies and therapies targeting pathways affected by Ref-1/APE1 redox signaling. Additionally, Ref-1/APE1 plays a role in a variety of other indications, such as retinopathy, inflammation, and neuropathy. In this review, we discuss the functional consequences of activation of the Ref-1/APE1 node in cancer and other diseases, as well as potential therapies targeting Ref-1/APE1 and related pathways in relevant diseases. APX3330, a novel oral anticancer agent and the first drug to target Ref-1/APE1 for cancer is entering clinical trials and will be explored in various cancers and other diseases bringing bench discoveries to the clinic.en-USAttribution 3.0 United StatesAPE1CancerDNA DamageArticle