@article{6e464d5443854db3b498ea24cb551f67,
title = "Using a novel NQO1 bioactivatable drug, beta-lapachone (ARQ761), to enhance chemotherapeutic effects by metabolic modulation in pancreatic cancer",
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 (H2O2) 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.",
keywords = "cancer metabolism, experimental therapeutics, hyperpolarization, pancreatic cancer, β-lapachone",
author = "Beg, {Muhammad Shaalan} and Xiumei Huang and Silvers, {Molly A.} and Gerber, {David E.} and Joyce Bolluyt and Venetia Sarode and Farjana Fattah and Deberardinis, {Ralph J.} and Merritt, {Matthew E.} and Xie, {Xian Jin} and Richard Leff and Daniel Laheru and Boothman, {David A.}",
note = "Funding Information: Disease response and progression will be evaluated in this study using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Any patient who receives treatment on this protocol will be evaluable for toxicity. Toxicity will be assessed according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0. The most common adverse events noted with the MPACT study that resulted in a dose reduction, delay or withholding of chemotherapy was neutropenia and thrombocytopenia. We will follow standard recommended dose modifications for gemcitabine and nab-paclitaxel per the MPACT trial. Publisher Copyright: {\textcopyright} 2017 Wiley Periodicals, Inc.",
year = "2017",
month = jul,
day = "1",
doi = "10.1002/jso.24624",
language = "English (US)",
volume = "116",
pages = "83--88",
journal = "Journal of Surgical Oncology",
issn = "0022-4790",
publisher = "Wiley-Liss Inc.",
number = "1",
}