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Identification of the rational combination of two epigenetic inhibitors therapy in refractory AML using patient tumor derived ex vivo platform.

Background: Acute myeloid leukemia (AML) is a highly heterogenous hematological malignancy. Though there has been substantial progress in understanding of AML biology and identification of new therapeutic targets, treatment of AML has largely remained unchanged over the last couple of decades, with 40% patients not achieving remission with standard chemotherapies. Methods: In this study, we employed an ex-vivo tumor explant model (CANscript) to select a treatment course for AML patients. CANscript offers a comprehensive system that mimics patient tumor microenvironment. 31 AML patients tumors were analyzed to predict response to cytarabine. We next evaluated azacitidine and panobinostat alone and in combination, as alternate treatment regimens for cytarabine refractory tumors.