A potential predictive value of particularKRASmutation subtypes has also been postulated. Patients harboring the dominant G12CKRASmutation had shorter PFS and OS than those with non-G12CKRASmutations in a subgroup of 38 patients harboring a mutatedKRASgene and wild-typeEGFRgene who were treated wi...
inhibitors, respectively [126,127]. A potential concern with these agents is inhibition of wild type KRAS and ensuing toxicities, however, preclinical data show limited wild type inhibition. RMC-6236 is a non-selective RAS inhibitor that blocks interactions of multiple ‘ON’ RAS isoforms with dow...
Impact of subsequent therapies on outcome of the FIRE-3/AIO KRK0306 trial: first-line therapy with FOLFIRI plus cetuximab or bevacizumab in patients with KRAS wild-type tumors in metastatic colorectal cancer. J Clin Oncol. 2015;33(32):3718-3726. doi:10.1200/JCO.2015.61.2887PubMedGoogle ...
•Unliketheoverexpressionoftheimmunotherapytargethumanepidermalgrowthfactorreceptor2(HER2)inbreastcancerpatients,whichismostoftenconnectedwithanamplificationoftheHER2gene,thecorrelationofEGFRproteinlevelsandgeneamplificationandtheirmeaningforEGFRimmunotherapyresponseisstillcontroversial.AsalreadyshownforEGFRproteinexpression,we...
The structural similarity between the GDP-bound structures of an oncogenic A146T mutant of KRAS (1–169) containing iMet and wild-type KRAS (2–169) without the iMet suggests that the structure of Mg2+-free KRAS-GDP described here resembles the conformation of KRAS that exists in oncogenic...
Impact of subsequent therapies on outcome of the FIRE-3/AIO KRK0306 trial: first-line therapy with FOLFIRI plus cetuximab or bevacizumab in patients with KRAS wild-type tumors in metastatic colorectal cancer. J Clin Oncol. 2015;33(32):3718-3726.PubMedGoogle ScholarCrossref 19. Venook AP, ...
A VOC detected here in association with TP53 downregulation (being depleted in cells with wild-type TP53), 2-methylpentane has previously been detected in NCI-H2087 cells (Sponring et al, 2009b), a lung adenocarcinoma cell line with mutated TP53. This may imply a possible biochemical pathway...
Thus, RAS(ON) multi-selective inhibitors can target multiple oncogenic and wild-type RAS isoforms and have the potential to treat a wide range of RAS-addicted cancers with high unmet clinical need. A related RAS(ON) multi-selective inhibitor, RMC-6236, is currently under clinical evaluation in...
et al. Impact of specific mutant KRAS on clinical outcome of EGFR-TKI-treated advanced non-small cell lung cancer patients with an EGFR wild type genotype. Lung Cancer 78, 81–86, doi: 10.1016/j.lungcan.2012.06.005 (2012). 19. Woo, J., Palmisiano, N., Tester, W. & Leighton, J....
(3 wild-type [WT], 6 SNORD50A/B KO), a fusion of the BirA* promiscuous biotin ligase to KRAS was expressed at physiologic levels in an N-terminal design that preserves Ras function and localization27(Supplementary Fig.1A–E). Since the KRAS4B isoform is the more common variant ...