decitabine + venetoclax + navitoclax

**Decitabine + venetoclax + navitoclax** is an investigational combination regimen composed of three agents used for the treatment of certain advanced or high-risk hematologic malignancies, notably acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). - **Decitabine** is a hypomethylating agent (a DNA methyltransferase inhibitor) that induces DNA hypomethylation, leading to the re-expression of silenced genes and apoptosis in malignant cells. - **Venetoclax** is an orally administered small molecule that selectively inhibits BCL-2, an anti-apoptotic protein often overexpressed in malignant cells, promoting cancer cell death. - **Navitoclax** is an orally administered small molecule inhibitor of the BCL-2 family (specifically BCL-2, BCL-xL, and BCL-w), acting via a similar but broader pathway than venetoclax, and is designed to overcome resistance mechanisms in cancer cells. The combination targets both apoptotic resistance (via BCL-2 and BCL-xL inhibition) and aberrant epigenetic regulation (via decitabine). This triplet therapy is being evaluated in phase 1 and 2 clinical trials for relapsed or refractory AML and higher-risk MDS following standard therapies, particularly in patients refractory to hypomethylating agents and/or venetoclax[1][2][3][4][5][6][7][9][10].