ArticleCancer discovery2024
Sotorasib Is a Pan-RASG12C Inhibitor Capable of Driving Clinical Response in NRASG12C Cancers.
Article in Cancer discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
31 citing papers in PubMed, 38 citations in OpenAlex.
- HRAS promotes mutant NRAS-driven transformation with codon and allele specificity.Science signaling · 2026Article
- Sphingosine-1-phosphate receptor modulators resensitize FLT3-ITD acute myeloid leukemia cells with NRAS mutations to FLT3 inhibitors.Leukemia · 2026Article
- Expanding Addressable KRAS Mutations through the Structure- and Property-Based Design of Dual-State (GDP/GTP), Reversible Pan-KRAS Inhibitors.Journal of medicinal chemistry · 2026Article
- Article
- Activity of Direct KRAS(G12C) Inhibitors in Preclinical Models of Pediatric Cancer.Molecular cancer therapeutics · 2026Article
- A catalogue of missense and nonsense mutation abundances for the U.S. cancer patient population.medRxiv : the preprint server for health sciences · 2026Article
- Review
- Targeting the NF-κB pathway represents a potential strategy to attenuate HGF-induced resistance to KRAS G12C inhibitors in lung adenocarcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Clinical Significance and Potential Molecular Mechanisms of Angiotensin-Converting Enzyme 2 in Colorectal Cancer.World journal of oncology · 2026Article
- RAS(ON) Multiselective Inhibition Drives Antitumor Immunity in Preclinical Models of NRAS-Mutant Melanoma.Cancer immunology research · 2026Article
- Melanoma: Pathogenesis and Targeted Therapy.MedComm · 2026Review
- Oncogenic KRAS mutations drive immune suppression through immune-related regulatory network and metabolic reprogramming.Cell death & disease · 2025Review
- RAS Pathway Inhibitors Combined with Targeted Agents Are Active in Patient-Derived Spheroids with Oncogenic KRAS Variants from Multiple Cancer Types.Cancer research communications · 2025Article
- Medicinal chemistry perspectives on anticancer drug design based on clinical applications (2015-2025).RSC advances · 2025Review
- Review
- Wild-type RAS signaling is an essential therapeutic target inScience signaling · 2025Article
- Current landscape of innovative drug development and regulatory support in China.Signal transduction and targeted therapy · 2025Review
- Binding modes of the KRAS(G12C) inhibitors GDC-6036 and LY3537982 revealed by all atom molecular dynamics simulations.Scientific reports · 2025Article
- Genomic landscape of clinically acquired resistance alterations in patients treated with KRASAnnals of oncology : official journal of the European Society for Medical Oncology · 2025Article
- Glecirasib, a Potent and Selective Covalent KRAS G12C Inhibitor Exhibiting Synergism with Cetuximab or SHP2 Inhibitor JAB-3312.Cancer research communications · 2025Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
KRASG12C inhibitors, like sotorasib and adagrasib, potently and selectively inhibit KRASG12C through a covalent interaction with the mutant cysteine, driving clinical efficacy in KRASG12C tumors. Because amino acid sequences of the three main RAS isoforms-KRAS, NRAS, and HRAS-are highly similar, we hypothesized that some KRASG12C inhibitors might also target NRASG12C and/or HRASG12C, which are less common but critical oncogenic driver mutations in some tumors. Although some inhibitors, like adagrasib, were highly selective for KRASG12C, others also potently inhibited NRASG12C and/or HRASG12C. Notably, sotorasib was five-fold more potent against NRASG12C compared with KRASG12C or HRASG12C. Structural and reciprocal mutagenesis studies suggested that differences in isoform-specific binding are mediated by a single amino acid: Histidine-95 in KRAS (Leucine-95 in NRAS). A patient with NRASG12C colorectal cancer treated with sotorasib and the anti-EGFR antibody panitumumab achieved a marked tumor response, demonstrating that sotorasib can be clinically effective in NRASG12C-mutated tumors. SIGNIFICANCE: These studies demonstrate that certain KRASG12C inhibitors effectively target all RASG12C mutations and that sotorasib specifically is a potent NRASG12C inhibitor capable of driving clinical responses. These findings have important implications for the treatment of patients with NRASG12C or HRASG12C cancers and could guide design of NRAS or HRAS inhibitors. See related commentary by Seale and Misale, p. 698. This article is featured in Selected Articles from This Issue, p. 695.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.