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The effectiveness of RAS/MAPK inhibitors in treating metastatic KRAS-mutant NSCLC is often hindered by the development of resistance driven by disrupted negative feedback mechanisms led by phosphatases like PP2A. PP2A is frequently suppressed in lung cancer to maintain elevated RAS/MAPK...
Benjamin Herzberg: The Impact of Eligibility Criteria on KRAS G12C Inhibitor Trials in NSCLC / Anjali Saqi, Benjamin May, Benjamin O. Herzberg, Brian S Benjamin Herzberg/LinkedIn Benjamin Herzberg: The Impact of Eligibility Criteria on KRAS G12C Inhibitor Trials in NSCLC...
Background KRASG12C alterations are present in ~13% of lung adenocarcinomas. AZD4625 is a covalent small molecule inhibitor that selectively binds and inhibits GDP-KRASG12C, leading to reduced cell viability and protein signaling responsible for tumor survival in models with this gain-of-function...
Distribution of immune cells across KRAS variants (A) B cells. (B) M1 macrophages. (C) M2 macrophages. (D) NK cells (E) CD8 T cells. (F) Treg cells. Statistical analysis indicates pairwise comparisons. Only q-values Introduction and Hypothesis Mutations in the KRAS...
“any of the responses occurred very early and remained sustained in this patient population,” said study presenter Chee Khoon Lee, MBBS, PhD First-line treatment with sotorasib, bevacizumab, and chemotherapy demonstrated activity in patients with KRAS G12C-mutant, advanced non-small cell lung...
Resistance to inactive state-selective RASG12C inhibitors frequently entails accumulation of RASGTP, rendering effective inhibition of active RAS potentially desirable. Here, we evaluated the antitumor activity of the RAS(ON) multiselective tricomplex inhibitor RMC-7977 and dissected mechanisms of response and tolerance in...
The FDA has granted breakthrough therapy designation to olomorasib in combination with pembrolizumab (Keytruda) for the treatment of unresectable advanced or metastatic non–small cell lung cancer (NSCLC) harboring a KRAS G12C mutation and PD-L1 expression ≥50%.1 This designation is supported...