The therapeutic approach for acute myeloid leukemia (AML) remains challenging, since over the last four decades a stagnation in standard cytotoxic treatment has been observed. But within recent years, remarkable advances in the understanding of the molecular heterogeneity and complexity of this disease have led to the identification of novel therapeutic targets. In the last two years, seven new targeted agents (midostaurin, gilteritinib, enasidenib, ivosidenib, glasdegib, venetoclax and gemtuzumab ozogamicin) have received US Food and Drug Administration (FDA) approval for the treatment of AML. These drugs did not just prove to have a clinical benefit as single agents but have especially improved AML patient outcomes if they are combined with conventional therapy. In this review, we will focus on currently approved and promising upcoming agents and we will discuss controversial aspects and limitations of targeted treatment strategies.

With the cancer stem cell (CSC) hypothesis many questions regarding cancer development and drug resistance can be answered more coherently than with the traditional model based on clonal evolution. CSCs are a small subset of cancer cells within the tumour that show stem cell characteristics like self-renewal, the capability to develop into multiple lineages and the potential to proliferate extensively, and are characterised by a typical profile of different markers like CD44 and CD133. In the CSC model, the role of embryonic pathways like Wnt, Hedgehog and Notch is of special interest. This review presents current scientific knowledge on this topic and discusses the potential role of CSC in the resistance against chemotherapy or radiation and presents challenging options for therapeutic interventions.