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Targeting eNOS in pancreatic cancer.

Publication ,  Journal Article
Lampson, BL; Kendall, SD; Ancrile, BB; Morrison, MM; Shealy, MJ; Barrientos, KS; Crowe, MS; Kashatus, DF; White, RR; Gurley, SB; Cardona, DM ...
Published in: Cancer Res
September 1, 2012

Mortality from pancreatic ductal adenocarcinoma cancer (PDAC) is among the highest of any cancer and frontline therapy has changed little in years. Activation of endothelial nitric oxide synthase (eNOS, NOS3, or NOS III) has been implicated recently in the pathogenesis of PDACs. In this study, we used genetically engineered mouse and human xenograft models to evaluate the consequences of targeting eNOS in PDACs. Genetic deficiency in eNOS limited the development of preinvasive pancreatic lesions and trended toward an extended lifespan in mice with advanced pancreatic cancer. These effects were also observed upon oral administration of the clinically evaluated NOS small molecule inhibitor N(G)-nitro-L-arginine methyl ester (l-NAME). Similarly, other transgenic models of oncogenic KRas-driven tumors responded to l-NAME treatment. Finally, these results were recapitulated in xenograft models of human pancreatic cancer, in which l-NAME was found to broadly inhibit tumorigenic growth. Taken together, our findings offer preclinical proof-of-principle to repurpose l-NAME for clinical investigations in treatment of PDACs and possibly other KRas-driven human cancers.

Duke Scholars

Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

September 1, 2012

Volume

72

Issue

17

Start / End Page

4472 / 4482

Location

United States

Related Subject Headings

  • ras Proteins
  • Xenograft Model Antitumor Assays
  • Tumor Burden
  • Stromal Cells
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • Nitric Oxide Synthase Type III
  • NG-Nitroarginine Methyl Ester
  • Mice, Transgenic
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Lampson, B. L., Kendall, S. D., Ancrile, B. B., Morrison, M. M., Shealy, M. J., Barrientos, K. S., … Counter, C. M. (2012). Targeting eNOS in pancreatic cancer. Cancer Res, 72(17), 4472–4482. https://doi.org/10.1158/0008-5472.CAN-12-0057
Lampson, Benjamin L., S Disean Kendall, Brooke B. Ancrile, Meghan M. Morrison, Michael J. Shealy, Katharine S. Barrientos, Matthew S. Crowe, et al. “Targeting eNOS in pancreatic cancer.Cancer Res 72, no. 17 (September 1, 2012): 4472–82. https://doi.org/10.1158/0008-5472.CAN-12-0057.
Lampson BL, Kendall SD, Ancrile BB, Morrison MM, Shealy MJ, Barrientos KS, et al. Targeting eNOS in pancreatic cancer. Cancer Res. 2012 Sep 1;72(17):4472–82.
Lampson, Benjamin L., et al. “Targeting eNOS in pancreatic cancer.Cancer Res, vol. 72, no. 17, Sept. 2012, pp. 4472–82. Pubmed, doi:10.1158/0008-5472.CAN-12-0057.
Lampson BL, Kendall SD, Ancrile BB, Morrison MM, Shealy MJ, Barrientos KS, Crowe MS, Kashatus DF, White RR, Gurley SB, Cardona DM, Counter CM. Targeting eNOS in pancreatic cancer. Cancer Res. 2012 Sep 1;72(17):4472–4482.

Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

September 1, 2012

Volume

72

Issue

17

Start / End Page

4472 / 4482

Location

United States

Related Subject Headings

  • ras Proteins
  • Xenograft Model Antitumor Assays
  • Tumor Burden
  • Stromal Cells
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • Nitric Oxide Synthase Type III
  • NG-Nitroarginine Methyl Ester
  • Mice, Transgenic
  • Mice