Co-targeting KRAS G12C and EGFR reduces both mutant and wild …
Nov 23, 2022 · The combination of KRAS G12C inhibitors with EGFR inhibitors has reproducibly been shown to be beneficial. Here, we identify another benefit of this combination: it effectively inhibits both...
RTK-mediated feedback activation of wild-type NRAS and HRAS bypasses KRASG12C. Inhibitor combinations abrogate RAS reactivation, boosting efficacy in KRASG12CCRC. Targeting convergent signaling nodes overcomes adaptive resistance by multiple RTKs. Ryan et al., 2022, Cell Reports , 110993. 39 June 21, 2022 2022 The Author(s).
A single inhibitor for all KRAS mutations | Nature Cancer
Aug 24, 2023 · Recent clinical data with KRAS inhibitors that are selective for KRAS (G12C) due to a covalent interaction with the mutant cysteine residue, have demonstrated favorable response rates in...
The promise and peril of KRAS G12C inhibitors - Cell Press
Aug 9, 2021 · Recent findings published in the New England Journal of Medicine show that sotorasib provides clinical benefit for KRAS p.G12C-mutated non-small-cell lung cancer (NSCLC) and provide mechanistic insights into acquired resistance to KRAS G12C -specific inhibition.
Targeting KRAS(G12C): From Inhibitory Mechanism to Modulation of ...
How does KRAS(G12C) hydrolyze sufficient GTP to enable cycling in cancer cells? The consensus view from recent reviews is that KRAS(G12C) is unique among KRAS oncoproteins in that it has a high intrinsic GTP hydrolysis rate.
Diverse alterations associated with resistance to KRAS (G12C ...
Nov 10, 2021 · In preclinical patient-derived xenograft and cell line models, resistance to KRAS(G12C) inhibition was associated with low allele frequency hotspot mutations in KRAS(G12V or G13D), NRAS(Q61K or...
Unraveling (K)RAS in pancreatic ductal adenocarcinoma
2 days ago · Mutant selective inhibitors Targeting KRAS G12C. Although the KRAS G12C mutation is found in only 1.6% of PDAC patients, it is the only KRAS mutation for which selective inhibitors have reached clinical application. Historically, the KRAS protein was considered “undruggable” until 2013, when Shokat and colleagues identified a novel cysteine-containing switch II pocket in KRAS G12C [7, 8].
Sotorasib Is a Pan-RASG12C Inhibitor Capable of Driving Clinical ...
May 1, 2024 · Because amino acid sequences of the three main RAS isoforms—KRAS, NRAS, and HRAS—are highly similar, we hypothesized that some KRAS G12C inhibitors might also target NRAS G12C and/or HRAS G12C, which are less common but critical oncogenic driver mutations in some tumors.
Motif-guided identification of KRAS-interacting proteins
4 days ago · These inhibitor function by forming a covalent bond with cysteine 12 of KRAS G12C, thereby locking KRAS in its inactive state [19, 20 ... Additional file 1: Fig. S1 Alignments of predicted complex structure of KRAS, HRAS, and NRAS bound to BRAF. KRAS, HRAS, NRAS, and BRAF are represented by wheat, sky blue, plum, and cornflower blue cartoon ...
Specific targeting of the KRAS mutational landscape in myeloma as …
Nov 4, 2021 · AZD4785 is a first-in-class next-generation cEt ASO compound that selectively targets and downregulates KRAS mRNA, leading to silencing of the related protein. It acts as a selective KRAS inhibitor, without activity against NRAS or HRAS.