Treatment with the nitric oxide synthase inhibitor L-NAME provides a survival advantage in a mouse model of Kras mutation-positive, non-small cell lung cancer.

Published

Journal Article

Oncogenic mutations in the gene KRAS are commonly detected in non-small cell lung cancer (NSCLC). This disease is inherently difficult to treat, and combinations involving platinum-based drugs remain the therapeutic mainstay. In terms of novel, pharmacologically actionable targets, nitric oxide synthases (NOS) have been implicated in the etiology of KRAS-driven cancers, including lung cancer, and small molecular weight NOS inhibitors have been developed for the treatment of other diseases. Thus, we evaluated the anti-neoplastic activity of the oral NOS inhibitor L-NAME in a randomized preclinical trial using a genetically engineered mouse model of Kras and p53 mutation-positive NSCLC. We report here that L-NAME decreased lung tumor growth in vivo, as assessed by sequential radiological imaging, and provided a survival advantage, perhaps the most difficult clinical parameter to improve upon. Moreover, L-NAME enhanced the therapeutic benefit afforded by carboplatin chemotherapy, provided it was administered as maintenance therapy after carboplatin. Collectively, these results support the clinical evaluation of L-NAME for the treatment of KRAS mutation-positive NSCLC.

Full Text

Duke Authors

Cited Authors

  • Pershing, NLK; Yang, C-FJ; Xu, M; Counter, CM

Published Date

  • July 5, 2016

Published In

Volume / Issue

  • 7 / 27

Start / End Page

  • 42385 - 42392

PubMed ID

  • 27285753

Pubmed Central ID

  • 27285753

Electronic International Standard Serial Number (EISSN)

  • 1949-2553

Digital Object Identifier (DOI)

  • 10.18632/oncotarget.9874

Language

  • eng

Conference Location

  • United States