NF-κB: A Druggable Target in Acute Myeloid Leukemia

Abstract

Acute Myeloid Leukemia (AML) is an aggressive hematological malignancy that relies on highly heterogeneous cytogenetic alterations. Although in the last few years new agents have been developed for AML treatment, the overall survival prospects for AML patients are still gloomy and new therapeutic options are still urgently needed. Constitutive NF-κB activation has been reported in around 40% of AML patients, where it sustains AML cell survival and chemoresistance. Given the central role of NF-κB in AML, targeting the NF-κB pathway represents an attractive strategy to treat AML. This review focuses on current knowledge of NF-κB's roles in AML pathogenesis and summarizes the main therapeutic approaches used to treat NF-κB-driven AML.

Keywords: NF-κB; NF-κB inhibitors; acute myeloid leukemia; cancer therapy; targeted therapy.

Figure 1

NF-κB activity in AML. Constitutive activation of NF-κB in AML triggered by (i) genetic alterations (blue), (ii) pro-inflammatory cytokines in the TME (fuchsia) and/or (iii) increased expression of NF-κB signaling components (green).

Figure 2

Targeting the NF-κB non-canonical pathway in AML. Schematic representation of the NF-κB non-canonical pathway showing that NIK stabilization suppresses tumor development and could be a potential strategy to treat AML.

Figure 3

Strategies for therapeutic inhibition of NF-κB canonical pathway in AML. Depicted is the mode of action of major NF-κB inhibitors that are in preclinical development or used in the clinic.