Meeting Report From the 2024 Symposium on IRAK4 in Cancer: Highlights and Clinical Updates.

Abstract

Interleukin-1 receptor-associated kinase 4 (IRAK4) is a serine/threonine kinase that mediates interleukin-1 and Toll-like receptor (TLR) signaling. IRAK4 drives the activation of nuclear factor kappa B (NF-κB), which promotes cell survival, inflammation, and proliferation. Aberrant activation of IRAK4 and TLR signaling has been implicated in multiple malignancies. At the 3rd Annual IRAK4 in Cancer Symposium, experts discussed the role of IRAK4 in cancer biology, the potential for synergism between IRAK4 inhibition and other treatments to overcome resistance, and how IRAK4 inhibition may improve clinical outcomes. Preclinical data were presented demonstrating the activity of IRAK4 inhibition alone or in combination with other anticancer agents in acute myeloid leukemia, myelodysplastic syndrome, non-Hodgkin lymphoma, primary central nervous system lymphoma, melanoma brain metastases, gastrointestinal cancers, and pancreatic ductal adenocarcinoma. Clinical data from the targeted small-molecule IRAK4 inhibitor emavusertib (CA-4948) were presented, including data from the TakeAim Leukemia and TakeAim Lymphoma trials of emavusertib in myeloid and lymphoid malignancies, respectively, and preliminary data from trials of emavusertib in multiple solid tumors. The meeting closed with expert discussion of the emerging profile of IRAK4 inhibition in cancers and the potential for IRAK4 inhibition to improve outcomes across both solid and liquid tumors.