BLOOD CANCER
Epigenetic Therapy Cancer Treatment
Epigenetic Therapy: A Breakthrough in Blood Cancer Treatment
Epigenetic drugs, including hypomethylating agents and HDAC inhibitors, represent the first therapeutic agents to exploit epigenetic alterations for improved patient outcomes. Decitabine, a derivative of Azacitadine, became the very first FDA-approved epigenetic drug in cancer treatment. These agents have shown remarkable success in treating hematologic malignancies, particularly myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). In 2004, 5-aza received FDA approval after demonstrating significant response rates in MDS patients, reduced risk of leukemic transformation, and increased survival. The landmark AZA-001 clinical study further established 5-aza as the preferred treatment for high-risk MDS patients.
Leukemias and lymphomas can be treated durably with epigenetic therapies, contrasting sharply with cytotoxic drugs that primarily stimulate cancer stem cells and make tumor recurrence nearly inevitable. This durability of response is crucial, as even the most sophisticated targeted therapies at leading research platforms struggle with long-term effectiveness. More recent additions to the market include EZH2 inhibitors, which target mutations found throughout the EZH2 gene—mutations associated with adverse prognosis. While EZH2 commonly functions as an oncogene, in myeloid neoplasia it can also act as a tumor suppressor. Many hematopoietic tumors carry genetic alterations leading to increased lysine 27 methylation, making them potentially responsive to EZH2 inhibitor therapies.
The Promise of MTET: Next-Generation Epigenetic Treatment
While epigenetic drugs were long considered the holy grail for treating solid tumors, they have unfortunately failed to provide superior outcomes in many studies. Even in hematological cancers where they show promise, tumors generally become refractory because these agents are unselective in their DNA-level mechanisms. For example, decitabine not only demethylates oncosuppressor genes but also affects oncopromoters such as S100B, which explains the drug's own carcinogenic potential. This limitation has driven the need for more selective and sophisticated epigenetic therapies.
One of the foundation's primary projects involves clinical trials for the novel Modified Multi Molecular Targeted Epigenetic Therapy (MTET), which represents a significant advancement in several ways. First, if optimized and approved, MTET can selectively affect oncosuppressor genes without unleashing cancer promoter genes, unlike traditional epigenetic drugs. Second, MTET combines desirable histone epigenetic effects with DNA epigenetic effects simultaneously—a long-standing goal in epigenetic therapy development. Finally, MTET offers flexible potency that addresses the dynamic epigenetic platform of cancer aberrancies. Notably, MTET also targets the important EZH2 gene, positioning it as a comprehensive approach to epigenetic cancer treatment with the potential to overcome current therapy limitations.