An expert overview of emerging therapies for acute myeloid leukemia: novel small molecules targeting apoptosis, p53, transcriptional regulation and metabolism

Introduction: Acute myeloid leukemia (AML) is an aggressive malignancy of clonal myeloid precursor cells. Curative therapy has classically involved the use of intensive induction chemotherapy followed by consolidation with additional chemotherapy or allogeneic hematopoietic stem cell transplant. For many patients, such an approach is prohibitive because of high treatment-related toxicities. Advancements in the molecular understanding of AML have led to the introduction of new targeted therapies that are changing the treatment landscape for AML. Areas covered: We review emerging small molecule inhibitors that have shown preclinical efficacy for the treatment of AML. The compounds discussed affect apoptosis, p53-mediated interactions, transcriptional regulation, and cellular metabolism. We performed a literature search of PubMed and primarily included relevant sources published from 2000 to the present, though earlier sources are also referenced. Expert opinion: Most clinical trials for AML currently employ novel targeted therapies that demonstrate promising activity in preclinical models. We anticipate that new small molecule inhibitors will continue to enter the clinical realm and alter the treatment paradigm for AML. In a field where clinical advancement was comparatively slow for many years, it appears that we are now starting to see the rapid growth borne out of the deepening molecular understanding of AML.