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:||
||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.|
Yves Pommier (NCI)
PCT Application No. PCT/US2006/029401
US Application No. 11/989,737
US Application No. 60/703,556
Jobson AG, et al. PMID 17616632
Jobson AG, et al. PMID 19741151
Lountos GT, et al. PMID 19177354
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 email@example.com for more information.
Uri Reichman , Ph.D., M.B.A.
NIH Office of Technology Transfer
OTT Reference No: E-211-2005/0