The tumor-suppressor p53 protein plays a major role in tumor development. Most human cancers fail to normally activate wild-type p53, which is at least partly responsible for the unregulated growth of cancer cells and their failure to undergo apoptosis. While many chemotherapeutics enhance p53 levels, their non-specific DNA damage (genotoxicity) causes unfavorable side effects.
Defects in the pathways that control the stabilization and activation of p53 in response to stress can contribute to cancer development, without the requirement for mutation within the p53 gene itself. Many tumors that retain wild-type p53 show evidence of alterations that prevent efficient activation of p53 in response to stress, linked to a failure to inactivate HDM2. In these tumors, inhibition of HDM2 and reactivation of p53 is an attractive therapeutic strategy. Researchers at the National Cancer Institute (NCI) have developed a water-soluble, small molecule inhibitor of HDM2’s E3 activity resulting in activation of p53 in tumors that retain wild-type p53.
This invention does not lead to the genotoxicity commonly observed when using other therapeutics directed at activating p53, making it an attractive option for cancer therapy. The NCI is seeking statements of capability or interest from parties interested in licensing or in collaborative research to co-develop technologies that inhibit HDM2’s activity and reactivate p53 activity for the treatment of cancer.
- Reduced genotoxicity compared to many chemotherapeutics
- Water-soluble with improved potency in stabilizing p53 and activating a p53 response
- Targeted therapies for activating wild-type p53 in tumors to induce apoptosis
- Inhibits unregulated growth of cancer cells