Journal article
Using a novel NQO1 bioactivatable drug, beta-lapachone (ARQ761), to enhance chemotherapeutic effects by metabolic modulation in pancreatic cancer
Journal of surgical oncology, Vol.116(1), pp.83-88
07/2017
DOI: 10.1002/jso.24624
PMCID: PMC5509448
PMID: 28346693
Abstract
Novel, tumor-selective therapies are needed to increase the survival rate of pancreatic cancer patients. K-Ras-mutant-driven NAD(P)H:quinone oxidoreductase 1 (NQO1) is over-expressed in pancreatic tumor versus associated normal tissue, while catalase expression is lowered compared to levels in associated normal pancreas tissue. ARQ761 undergoes a robust, futile redox cycle in NQO1+ cancer cells, producing massive hydrogen peroxide (H O ) levels; normal tissues are spared by low NQO1 and high catalase expression. DNA damage created by ARQ761 in pancreatic cancer cells "hyperactivates" PARP1, causing metabolic catastrophe and NAD ± keresis cell death. NQO1: catalase levels (high in tumor, low in normal tissue) are an attractive therapeutic window to treat pancreatic cancer. Based on a growing body of literature, we are leading a clinical trial to evaluate the combination of ARQ761 and chemotherapy in patients with pancreatic cancer.
Details
- Title: Subtitle
- Using a novel NQO1 bioactivatable drug, beta-lapachone (ARQ761), to enhance chemotherapeutic effects by metabolic modulation in pancreatic cancer
- Creators
- Muhammad Shaalan Beg - Harold Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TexasXiumei Huang - Departments of Pharmacology and Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TexasMolly A Silvers - Harold Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TexasDavid E Gerber - Harold Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TexasJoyce Bolluyt - Harold Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TexasVenetia Sarode - Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TexasFarjana Fattah - Harold Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TexasRalph J Deberardinis - Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TexasMatthew E Merritt - Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FloridaXian-Jin Xie - Harold Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TexasRichard Leff - Clinical Pharmacology & Experimental Therapeutics Center, Texas Tech University Health Sciences Center, School of Pharmacy, Dallas, TexasDaniel Laheru - Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MarylandDavid A Boothman - Departments of Pharmacology and Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas
- Resource Type
- Journal article
- Publication Details
- Journal of surgical oncology, Vol.116(1), pp.83-88
- DOI
- 10.1002/jso.24624
- PMID
- 28346693
- PMCID
- PMC5509448
- NLM abbreviation
- J Surg Oncol
- ISSN
- 1096-9098
- eISSN
- 1096-9098
- Publisher
- United States
- Grant note
- K24 CA201543 / NCI NIH HHS P41 EB015908 / NIBIB NIH HHS P30 CA142543 / NCI NIH HHS R01 CA102792 / NCI NIH HHS R01 DK105346 / NIDDK NIH HHS
- Language
- English
- Date published
- 07/2017
- Academic Unit
- Preventive and Community Dentistry; Biostatistics; Dental Research
- Record Identifier
- 9983917770502771
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