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.
Original language | English (US) |
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Pages (from-to) | 83-88 |
Number of pages | 6 |
Journal | Journal of Surgical Oncology |
Volume | 116 |
Issue number | 1 |
DOIs |
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State | Published - Jul 1 2017 |
Keywords
- cancer metabolism
- experimental therapeutics
- hyperpolarization
- pancreatic cancer
- β-lapachone
ASJC Scopus subject areas
- Surgery
- Oncology