Publications by authors named "Allan Hebbert"
KRAS is the most frequently mutated oncogene in human cancer and facilitates uncontrolled growth through hyperactivation of the receptor tyrosine kinase (RTK)/mitogen-activated protein kinase (MAPK) pathway. The Son of Sevenless homolog 1 (SOS1) protein functions as a guanine nucleotide exchange factor (GEF) for the RAS subfamily of small GTPases and represents a druggable target in the pathway. Using a structure-based drug discovery approach, MRTX0902 was identified as a selective and potent SOS1 inhibitor that disrupts the KRAS:SOS1 protein-protein interaction to prevent SOS1-mediated nucleotide exchange on KRAS and translates into an anti-proliferative effect in cancer cell lines with genetic alterations of the KRAS-MAPK pathway.
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- Previous research highlighted PRMT5 as a target for treating cancers lacking the MTAP gene (MTAP del), but effective small-molecule inhibitors like MRTX1719 were not fully explored until now.
- MRTX1719 specifically inhibits PRMT5 activity in the presence of elevated MTA found in MTAP del cancers, showing significant anti-tumor effects and selective efficacy in cancer cells with MTAP deletions.
- Early clinical trials indicate that MRTX1719 may help patients with various cancers carrying the MTAP deletion, representing a promising treatment option for about 10% of cancer patients with this specific genetic marker.