Evripidis Gavathiotis

Abstract Endosomal function is essential for pattern recognition receptor signaling, through endosomal Toll-like receptor (TLR) sensing of nonself RNA and DNA. The specific interaction of the calcium sensor Munc13-4 with syntaxin 7 (STX7) regulates endosomal flux and Munc13-4 depletion decreases the systemic inflammatory response to unmethylated DNA.

Abstract Acute myeloid leukemia (AML) is an aggressive myeloid malignancy with a poor prognosis. Venetoclax (Ven), a BCL2 inhibitor, has shown promising results but often leads to relapse due to mitochondrial dysregulation, particularly due to upregulation of the anti-apoptotic protein MCL1. Overexpression of the transcription factor STAT3 has been linked to poor survival in AML patients.

RAS–MAPK pathway inhibitors are limited by pathway reactivation and toxicity. A study now introduces IK-595, a MEK–RAF molecular glue that stabilizes MEK in an inactive complex with RAF isoforms, enabling durable inhibition of ERK signaling and anti-tumor activity in various cancers in which RAS or RAF is altered, including those resistant to current standard-of-care therapies.