Invention Novelty
This invention is a novel paradigm for the induction of synthetic lethality through epigenetic modulations. This can induce functionality and efficacy of therapeutics against cancer cells that may have resistance to each therapeutic alone.
Value Proposition
The complex and adaptive nature of the host of diseases termed cancer poses significant challenges. Many therapeutics which confer an initial benefit to patients may fail to maintain efficacy as the disease develops resistance mechanisms. This challenge can render otherwise effective drugs useless for an indicated disease. This invention is a paradigm for the re-sensitization of cancer cells to anti-cancer agents. The inventors have demonstrated that existing pharmacological agents can alter render cancer cells susceptible to therapeutics to which resistance has occurred.
Advantages include:
· Restoration of efficacy for a therapeutic that fails as a single agent
· Induction of selective efficacy against cancer cells over healthy host cells
· Persistence of sensitization after removal of the epigenetic agent
· Changes are seen with low-dose, sub-cytotoxic amounts of agent
Technology Details
This paradigm makes use of a pharmacological or genetic agent that can alter the epigenetic machinery for the epigenetic “reprogramming” of cancer cells. Through these changes it is possible to induce new vulnerabilities to targeted therapeutics which would otherwise be ineffective. The work by the inventors has demonstrated the establishment and maintenance of the appropriate epigenetic marks, including DNA methylation, at regions critical for chromosomal integrity can produce mitotic catastrophe (i.e. cell death) in cancer cells through epigenetic dysregulation. This paradigm holds promise as a novel treatment approach for cancer that can allow for the use of targeted agents that might otherwise have failed as single agents.
Stage of Development
Preclinical. Validated in vivo and in vitro.
Publications
WO 2018/226802
