Radiation Sensitization Agents for Prostate Cancer

Invention novelty: A new mechanism to selectively sensitize the prostate to radiation therapy by knocking down DNA repair gene transcripts.

• Value Proposition: Current dose-escalated radiation therapy for localized prostate cancer treatment has increased the risk of injury of surrounding non-cancerous tissue due to its non-targeting application. Thus, there is a great need for the development of tissue-selective and radiation-sensitizing agents. This technology can solve the problem of broad or non-selective radiation and improve the result of radiation therapy in localized and metastatic prostate cancer. The other advantages include:Higher tissue-selective targeting
• Lower levels of ionizing radiation
• Fewer adverse effects from injury to surrounding normal tissues

Technical Details:Johns Hopkins researchers have identified six target genes in DNA-repair pathway for prostate cancer radiation sensitization by performing a high-throughput siRNA screen. They found these targets including DNA Protein Kinase and their corresponding siRNAs were conjugated to PSMA-targeting RNA aptamers in short-hairpin format (shRNA) and formed Aptamer-DNA-PK-shRNA chimeras which showed PSMA selective targeting to prostate cancer cells. In addition, intratumoral injection of the chimeras significantly showed specific gene knock-down and enhanced ionizing radiation therapeutic response in radiation therapy. They also found some similar results when they applied the same approach to human prostate tissue. Based on these results, they have demonstrated that radiation-sensitizing chimeras will effectively improve radiation therapy for high-risk localized prostate cancer.

Looking for Partners: To develop and commercialize the technology as a therapeutic agent which is used to selectively sensitize the prostate to radiation therapy

Stage of Development: Pre-Clinical

Data Availability: In vivo and In vitro data 

Patent Status: PCT WO 2012/012710

Publication(s)/Associated Cases: J Clin Invest. 2011 Jun;121(6):2383-90.