Sensitizing Cancer Cells to DNA Targeted Therapies


Chk2 is a protein kinase activated in response to DNA double strand breaks. In normal tissues, Chk2 phosphorylates and thereby activates substrates that induce programmed cell death, or apoptosis, via interactions with p53, E2F1, PML proteins. In cancer tissues, where apoptosis is suppressed, Chk2 phosphorylates and inactivates cell cycle checkpoints (via interactions with Cdc25, phosphatases and Brca1 proteins), which allows cancer cells to repair and tolerate DNA damage. Hence, Chk2 inhibitors would be expected to protect normal tissues by reducing apoptosis, and to sensitize cancer cells to DNA-targeted agents.

Potential Commercial Applications: Competitive Advantages:
  • Combination with DNA targeted chemotherapeutic agents for the treatment of cancers.
  • Single agents therapy for cancers with endogenously activated ("addicted to") Chk2.
  • Antiviral agent against hepatitis, herpes viruses and retroviral infections (HIV).
  Selective enhancement of the antiproliferative and proapoptotic activities of DNA targeted chemotherapeutic agents in tumors with inactivated p53, while protection of normal tissues by blocking p53-mediated apoptosis ("side effects") induced by the DNA targeted agents.


Inventors:
Yves Pommier (NCI)


Intellectual Property:
PCT Application No. PCT/US2006/029401
US Application No. 11/989,737
US Application No. 60/703,556

Publications:
Jobson AG, et al. PMID 17616632
Jobson AG, et al. PMID 19741151
Lountos GT, et al. PMID 19177354

Collaboration Opportunity:

The National Cancer Institute, Laboratory of Molecular Pharmacology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.


Licensing Contact:
Uri Reichman , Ph.D., M.B.A.
NIH Office of Technology Transfer
Email: reichmau@mail.nih.gov
Phone: 301-435-4616

OTT Reference No: E-211-2005/0

Updated: Jun-01-2012