Using a novel NQO1 bioactivatable drug, beta-lapachone (ARQ761), to enhance chemotherapeutic effects by metabolic modulation in pancreatic cancer

Muhammad Shaalan Beg, Xiumei Huang, Molly A. Silvers, David E. Gerber, Joyce Bolluyt, Venetia Sarode, Farjana Fattah, Ralph J. Deberardinis, Matthew E. Merritt, Xian Jin Xie, Richard Leff, Daniel Laheru, David A. Boothman

Research output: Contribution to journalArticle

9 Scopus citations


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.

Original languageEnglish (US)
JournalJournal of Surgical Oncology
Publication statusAccepted/In press - 2017



  • Cancer metabolism
  • Experimental therapeutics
  • Hyperpolarization
  • Pancreatic cancer
  • β-lapachone

ASJC Scopus subject areas

  • Surgery
  • Oncology

Cite this