Unmet Need
Genome stability is regulated by a variety of mechanisms. One such mechanism is DNA methylation. DNA methylation can alter the manner in which genes are expressed, and aberrations in methylation management are well documented as features of cancer cells. DNA methylation is regulated in part by enzymes known as DNA methyltransferases (DNMTs). Studies have shown that inhibiting DNMTs can induce anti-cancer processes. However, DNMT inhibitors (DNMTis) have thus far proven to have limited use. Some suggest that bioavailability, dose-dependent toxicity, and metabolic adaptations have prevented DMNTis from being effective cancer monotherapies. Therefore, there is a strong need to develop a more effective use of DNMTis as cancer therapeutics.
Value Proposition
- Synergistic interactions of combination therapies
- Favorable efficacy and safety in vitro and in vivo
- Overcomes cancer-cell intrinsic primary resistance to DNMT inhibitors
Technology Description
Researchers at Johns Hopkins have developed an effective therapeutic method to enhance the utility of DNA methyltransferase inhibitors. The therapeutic involves a unique combination of DNMTis with a previously identified terpenoid molecule. The combination therapy has successfully been shown to sensitize cancer cell lines to DNMTi treatment. This sensitization effect was demonstrated in multiple cancer types. Furthermore, the combination therapy successfully reduced prostate tumor growth in murine models without evidence of systemic toxicity
Stage of Development
Currently in preclinical stage of development. Seeking commercial partnerships or licensing to further develop early phase clinical trials.
Data Availability: Data available upon request.
Publications:
Liu, J., He, Q. L., Zhou, J., Chikarmane, R., Hauk, G., Rachakonda, A., ... & Yegnasubramanian, S. (2024). Triptolide sensitizes cancer cells to nucleoside DNA methyltransferase inhibitors through inhibition of DCTPP1-mediated cell-intrinsic resistance. bioRxiv, 2024-05.
