Nuclear factor κB as a target for new drug development in myeloid malignancies

Abstract

The transcription nuclear factor κ B (NF-κB) can intervene in oncogenesis through to its capacity to regulate the expression of a large number of genes that regulate apoptosis, cell proliferation and differentiation as well as inflammation, angiogenesis and tumor migration. Impaired NF-κB activity has been demonstrated not only in solid cancers but also in various types of hematologic malignancies including acute myeloid leukemia, chronic myelogenous leukemia and in a subset of myelodysplastic syndromes. The underlying mechanisms, illustrated in the text and although quite diverse in different diseases, provide the rationale for new therapeutic strategies combining different NF-κB or proteasome inhibitors. It has, therefore, been proposed that inhibition of NF-κB could be an adjuvant therapy for cancer and many phase I/II clinical studies are ongoing with different inhibitors. This review highlights the in vitro and in vivo results of NF-κB inhibition in myeloid malignancies. ©2007 Ferrata Storti Foundation.