Pyruvate as a Transient Hypoxia Inducer for Anti-cancer Therapies
Posted Jul 25 2011 8:00pm
Description of Invention: Human solid tumors, such as breast cancer, lung cancer, ovarian cancer, pancreatic cancer and prostate cancer, etc. frequently have substantial volumes with low oxygen concentration, i.e. hypoxic. These hypoxic tumors show resistance to radiation and chemotherapies. To overcome such resistance, novel classes of agents have been designed and developed that are specifically active or activated under hypoxic conditions, in hypoxic tumors. The instant invention describes a novel idea to improve anti-cancer effect of hypoxia-sensitive therapeutics by using a rapidly oxidized reducing agent such as pyruvate or succinate. In the instant invention, the NIH investigators found that pyruvate, an endogenous substrate for energy production by mitochondria, induced severe hypoxia in tumors within 30 minutes of intravenous injection, and the tumor oxygen level reversibly returned to basal level within a few hours. Since pyruvate seems to induce only transient hypoxia, and its safety profiles are known, it may have significant advantages over other hypoxia inducers reported to date for improving the efficacy of hypoxia-sensitive anti-cancer therapies.
Applications:
Provide a novel way to target various cancers, especially solid tumors for treatment;
Improve the efficacy of using hypoxic toxins for cancer treatment;
In vivo screening of oxygen-status dependent drugs.
Development Status: Pre-clinical stage of development.
Inventors: Shingo Matsumoto (NCI) James B Mitchell (NCI) Robert J Gillies (H. Lee Moffitt Cancer Center and Research Institut)
Poster presentation at the International Society for Magnetic Resonance in Medicine (ISMRM) meeting in May 2011. Manuscript is in press.
For Licensing Information Please Contact: Betty Tong Ph.D. NIH Office of Technology Transfer 6011 Executive Blvd. Suite 325, Rockville, MD 20852 United States Email: tongb@mail.nih.gov Phone: 301-594-6565 Fax: 301-402-0220
Description of Invention:
Human solid tumors, such as breast cancer, lung cancer, ovarian cancer, pancreatic cancer and prostate cancer, etc. frequently have substantial volumes with low oxygen concentration, i.e. hypoxic. These hypoxic tumors show resistance to radiation and chemotherapies. To overcome such resistance, novel classes of agents have been designed and developed that are specifically active or activated under hypoxic conditions, in hypoxic tumors. The instant invention describes a novel idea to improve anti-cancer effect of hypoxia-sensitive therapeutics by using a rapidly oxidized reducing agent such as pyruvate or succinate. In the instant invention, the NIH investigators found that pyruvate, an endogenous substrate for energy production by mitochondria, induced severe hypoxia in tumors within 30 minutes of intravenous injection, and the tumor oxygen level reversibly returned to basal level within a few hours. Since pyruvate seems to induce only transient hypoxia, and its safety profiles are known, it may have significant advantages over other hypoxia inducers reported to date for improving the efficacy of hypoxia-sensitive anti-cancer therapies.
Applications:
Development Status:
Pre-clinical stage of development.
Inventors:
Shingo Matsumoto (NCI)
James B Mitchell (NCI)
Robert J Gillies (H. Lee Moffitt Cancer Center and Research Institut)
Patent Status:
HHS, Reference No. E-144-2011/0
US, Application No. 61/478,465 filed 22 Apr 2011
Relevant Publication:
For Licensing Information Please Contact:
Betty Tong Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: tongb@mail.nih.gov
Phone: 301-594-6565
Fax: 301-402-0220
Ref No: 2286
Updated: 07/2011