Aminoglycosides and Ribosome Inhibitors as Inhibitors of Tyrosyl-DNA-Phosphodiesterase
Description of Invention:
Cancer has long been a leading cause of mortality in the United States. DNA-damaging therapies, such as radiotherapy and chemotherapy, are the methods of choice for treating subjects with metastatic cancer or subjects with diffuse cancers such as leukemias. However, radiotherapy can cause substantial damage to normal tissue in the treatment field, resulting in scarring and, in severe cases, loss of function of the normal tissue. Although chemotherapy can provide a therapeutic benefit in many cancer subjects, it often fails to treat the disease because cancer cells may become resistant to the chemotherapeutic agent. To overcome these limitations additional antineoplastic strategies, such as enhancing the antineoplastic effect of existing therapies, are needed.
This invention discloses a method for enhancing an antineoplastic effect of a DNA-damaging therapy. The method includes administering to a subject having a neoplasm a therapeutically effective amount of the DNA-damaging therapy and a ribosome inhibitor that inhibits tyrosyl-DNA phosphodiesterase 1 (Tdp1) activity, wherein the ribosome inhibitor is administered in a sufficient amount to enhance the DNA-damaging therapy.
This disclosure also provides pharmaceutical compositions that include at least one chemotherapeutic agent and at least one ribosome inhibitor that inhibits Tdp1 activity, wherein the chemotherapeutic agent and the ribosome inhibitor are present in a therapeutically effective amount for the ribosome inhibitor to enhance an antineoplastic effect of the chemotherapeutic agent.
Inventors:
Drs. Yves Pommier and Zhi-Yong Liao (NCI)
Patent Status:
DHHS Reference No. E-117-2005/0-US-01 -- U.S. Provisional Application No. 60/661,306 filed 11 Mar 2005 Licensing Status:
In addition to licensing, the technology is available for further development through collaborative research opportunities with the inventors.
Portfolios: Cancer
Cancer -Therapeutics-Conventional Chemotherapy Cancer -Therapeutics
For Additional Information Please Contact: John Stansberry Ph.D.
NIH Office of Technology Transfer
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: (301)435-5236
Email: stansbej@mail.nih.gov
Fax: (301) 402-0220
