Evidence map›Paper›PMID 28825044›Full record

ArticleNPJ precision oncology2017

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

Fenil Shah, Derek Logsdon, Richard A Messmann, Jill C Fehrenbacher, Melissa L Fishel, Mark R Kelley

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in NPJ precision oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03375086 (A Phase 1 Study of APX3330 in Patients With Advanced Solid Tumors), which is not on this map. Cited by 91 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
91citing papers in PubMed, 1 pooled it
4.6field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03375086 phase1completednot on this mapstarted 2018, after this paper: background citation

A Phase 1 Study of APX3330 in Patients With Advanced Solid Tumors

TypeinterventionalSponsorApexian Pharmaceuticals, Inc.Ran2018 to 2019Enrolled19ConditionsCancerArmsAPX3330
3 · Its place in the literature

Who cites it

91 citing papers in PubMed, 1 synthesis or guideline pooled it, 150 citations in OpenAlex.

  1. Pooled it
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  18. Proteomics in pancreatic cancer.Biomarker research · 2025
    Review
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31 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Fenil ShahDepartment of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 W. Walnut St., Indianapolis, IN 46202, USA.
Derek LogsdonDepartment of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 W. Walnut St., Indianapolis, IN 46202, USA.
Richard A MessmannApexian Pharmaceuticals, Indianapolis, IN 46204, USA.
Jill C FehrenbacherDepartment of Pharmacology & Toxicology, Indiana University School of Medicine, 1044 W. Walnut St., Indianapolis, IN 46202, USA.
Melissa L FishelDepartment of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 W. Walnut St., Indianapolis, IN 46202, USA.
Mark R KelleyDepartment of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 W. Walnut St., Indianapolis, IN 46202, USA.
Indiana University – Purdue University Indianapolis · USIndiana University School of MedicineApeX Therapeutics (United States) · US

Funding

Novel Role of Ref-1 in Pancreatic Cancer Etiology and ProgressionR01CA167291 · NCI · INDIANA UNIVERSITY INDIANAPOLIS · PI FISHEL, MELISSA L., KELLEY, MARK R. · 2013 to 2022
$5.2M
(PQ9)Mechanistic Role of APE1 and BER in chemotherapy-induced peripheral neuropathyR01CA205166 · NCI · INDIANA UNIVERSITY INDIANAPOLIS · PI FEHRENBACHER, JILL C, KELLEY, MARK R. · 2017 to 2021
$2.7M
The Role of Ape1 in Neurotoxicity of Cancer TreatmentsR01CA121168 · NCI · INDIANA UNIVERSITY INDIANAPOLIS · PI KELLEY, MARK R. · 2008 to 2012
$2.4M
Dual Targeting of DNA Repair and p53 pathways for treatment of brain cancerR01CA138798 · NCI · INDIANA UNIVERSITY INDIANAPOLIS · PI POLLOK, KAREN ELIZABETH · 2010 to 2014
$1.5M
DNA damage and repair in inflammation-induced peripheral sensitizationR21NS091667 · NINDS · INDIANA UNIVERSITY INDIANAPOLIS · PI FEHRENBACHER, JILL C, KELLEY, MARK R. · 2015 to 2016
$429k
Chemosensitization of Pancreatic Tumors via Inhibition of a DNA BER Enzyme, Ape1R21CA122298 · NCI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI FISHEL, MELISSA L. · 2007 to 2008
$333k
NCI NIH HHS R01 CA121168NCI NIH HHS R01 CA138798NCI NIH HHS R01 CA167291NCI NIH HHS R01 CA205166NCI NIH HHS R21 CA122298NINDS NIH HHS R21 NS091667
6 · The paper itself

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.

Identifiers

PMID28825044
PMCPMC5558897
OpenAlexW2618969102

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.