P53 and VGEF Regulate Tumor Growth of NO2 Expressing Cancer Cells
Description of Invention:
The increased expression of nitric oxide synthase 2 (NOS2), an inducible enzyme that produces nitric oxide (NO), has been found in a variety of human cancers. It also has been shown that NOS2-specific inhibitors can reduce the growth of experimental tumors in mice. These findings suggest a pathophysiological role for NO in the development and progression of cancer. However, the function of NO and NOS2 in carcinogenesis is uncertain. NO had been found to either inhibit or stimulate tumor growth, and high concentrations of NO also are known to induce cell death in many cell types including tumor cells. On the other hand, the lower concentrations of NO that are found in human tissue can have an opposite effect and protect against programmed cell death, or apoptosis, from various stimuli. The role of NO and NOS2 in tumor progression, particularly with respect to p53, therefore need to be further defined.
This invention comprises methods of screening for modulators of NOS2 expression in p53 mutant cells, both in vivo and in vitro, as well as methods for predicting the chemotherapeutic benefit of administering NOS2-inhibitors to cancer patients. It has been demonstrated that NOS2-expressing cancer cells with wild-type p53 have reduced tumor growth in athymic nude mice whereas NOS2-expressing cancer cells with mutated p53 have accelerated tumor growth. Therefore, this invention has potential application for a number of cancers that overexpress NOS2 and have a high frequency of p53 mutations, including breast, brain, head, neck, lung and colon cancers.
Applications:
Method to treat cancer with NOS2 inhibitors
Method to screen for NOS2 modulators
Method to predict therapeutic benefits of NOS2 inhibitors in patients
Market:
An estimated 1,444,920 new cancer diagnoses in the U.S. in 2007
600,000 deaths caused by cancer in the U.S. in 2006
Cancer is the second leading cause of death in United States
It is estimated that market for cancer drugs would double to $50 billion a year in 2010 from $25 billion in 2006
Development Status:
The technology is currently in the pre-clinical stage of development.
Patent Status:
DHHS Reference No. E-223-1998/0 --
U.S. Patent Application No. 11/195,006 filed 01 Aug 2005
U.S. Patent Application No. 09/830,977 filed 02 May 2001
PCT Patent Application No. PCT/US1999/27410 filed 17 Nov 1998
U.S. Provisional Patent Application No. 60/109,563 filed 23 Nov 1998
Relevant Publication:
JE Goodman et al. Nitric oxide and p53 in cancer-prone chronic inflammation and oxyradical overload diseases. Environ Mol Mutagen. 2004;44(1):3-9. [PubMed abs]
LJ Hofseth et al. Nitric oxide in cancer and chemoprevention. Free Radic Biol Med. 2003Apr 15;34(8):955-968. [PubMed abs]
Licensing Status: Available for exclusive or non-exclusive licensing.
Portfolios: Devices/Instrumentation Cancer
Cancer -Therapeutics Cancer -Other Devices/Instrumentation-Therapeutics
For Additional Information Please Contact: Jennifer Wong
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301)435-4633
Email: wongje@mail.nih.gov
Fax: (301)402-0220
