Exploiting the Ref-1-APE1 node in cancer signaling and other diseases: from bench to clinic

Abstract Reduction-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...

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Autores principales:	Fenil Shah, Derek Logsdon, Richard A. Messmann, Jill C. Fehrenbacher, Melissa L. Fishel, Mark R. Kelley
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/d4922a8724424a4aa80fa8db14f33c57
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spelling	oai:doaj.org-article:d4922a8724424a4aa80fa8db14f33c572021-12-02T13:41:45ZExploiting the Ref-1-APE1 node in cancer signaling and other diseases: from bench to clinic10.1038/s41698-017-0023-02397-768Xhttps://doaj.org/article/d4922a8724424a4aa80fa8db14f33c572017-06-01T00:00:00Zhttps://doi.org/10.1038/s41698-017-0023-0https://doaj.org/toc/2397-768XAbstract Reduction-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.Fenil ShahDerek LogsdonRichard A. MessmannJill C. FehrenbacherMelissa L. FishelMark R. KelleyNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Precision Oncology, Vol 1, Iss 1, Pp 1-19 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Fenil Shah Derek Logsdon Richard A. Messmann Jill C. Fehrenbacher Melissa L. Fishel Mark R. Kelley Exploiting the Ref-1-APE1 node in cancer signaling and other diseases: from bench to clinic
description	Abstract Reduction-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.
format	article
author	Fenil Shah Derek Logsdon Richard A. Messmann Jill C. Fehrenbacher Melissa L. Fishel Mark R. Kelley
author_facet	Fenil Shah Derek Logsdon Richard A. Messmann Jill C. Fehrenbacher Melissa L. Fishel Mark R. Kelley
author_sort	Fenil Shah
title	Exploiting the Ref-1-APE1 node in cancer signaling and other diseases: from bench to clinic
title_short	Exploiting the Ref-1-APE1 node in cancer signaling and other diseases: from bench to clinic
title_full	Exploiting the Ref-1-APE1 node in cancer signaling and other diseases: from bench to clinic
title_fullStr	Exploiting the Ref-1-APE1 node in cancer signaling and other diseases: from bench to clinic
title_full_unstemmed	Exploiting the Ref-1-APE1 node in cancer signaling and other diseases: from bench to clinic
title_sort	exploiting the ref-1-ape1 node in cancer signaling and other diseases: from bench to clinic
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/d4922a8724424a4aa80fa8db14f33c57
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Exploiting the Ref-1-APE1 node in cancer signaling and other diseases: from bench to clinic

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