ArticleScientific reports2022
Concomitant KRAS mutations attenuate sensitivity of non-small cell lung cancer cells to KRAS G12C inhibition.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 16 citations in OpenAlex.
- KRAS Inhibitor-Induced Cancer Cell Death Enhances Sensitivity to Immune-Mediated Bystander Killing of Drug-Resistant Subclones.Cancer research · 2026Article
- The clinicopathologic characteristics and outcomes of uncommon KRAS mutations in patients with non-small cell lung cancer.Virchows Archiv : an international journal of pathology · 2026Article
- SuperSelective PCR primers for determining cis/trans configurations of mutations within the same gene.PloS one · 2026Article
- Bracing for the storm: emerging resistance mechanisms to KRAS inhibitors in pancreatic cancer and strategies to overcome them.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- Sex-Related Safety Signals of Sotorasib in Non-Small Cell Lung Cancer: A Real-World, Pharmacovigilance Study from the EudraVigilance Database.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Novel paradigms in KRAS targeting: Unveiling strategies to combat drug resistance.Chinese medical journal · 2025Review
- [Advances in Immunotherapy of KRAS-mutated Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Review
- Utilizing ctDNA to discover mechanisms of resistance to targeted therapies in patients with metastatic NSCLC: towards more informative trials.Nature reviews. Clinical oncology · 2025Review
- Advances in the treatment of KRASCancer · 2025Review
- PD-1/L1 immune checkpoint inhibitors for KRAS-mutant non-small cell lung cancer: a multicenter retrospective real-world study.BMC cancer · 2025Article
- Spatial multiplex analysis of lung cancer reveals that regulatory T cells attenuate KRAS-G12C inhibitor-induced immune responses.Science advances · 2024Article
- Comparison between next-generation sequencing and multiplex polymerase chain reaction assays for nonsmall-cell lung cancer molecular diagnosis.Cancer medicine · 2024Article
- Kristen rat sarcoma virus (KRAS) G12F-positive non-small cell lung cancer mimicking KRAS G12C positivity: A case report.Thoracic cancer · 2024Article
- Article
- Drugging KRAS: current perspectives and state-of-art review.Journal of hematology & oncology · 2022Review
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development of covalent inhibitors against KRAS G12C represents a major milestone in treatment of RAS-driven cancers, especially in non-small cell lung cancer (NSCLC), where KRAS G12C is one of the most common oncogenic driver. Here we investigated if additional KRAS mutations co-occur with KRAS G12C (c.34G>T) in NSCLC tumours and if such mutation co-occurrence affects cellular response to G12C-specific inhibitors. Analysis of a large cohort of NSCLC patients whose tumours harboured KRAS mutations revealed co-occurring KRAS mutations in up to 8% of tumours with the KRAS c.34G>T mutation. KRAS c.35G>T was the most frequently co-occurring mutation, and could occur on the same allele (in cis) translating to a single mutant KRAS G12F protein, or on the other allele (in trans), translating to separate G12C and G12V mutant proteins. Introducing KRAS c.35G>T in trans in the KRAS G12C lung cancer model NCI-H358, as well as the co-occurrence in cis in the KRAS G12F lung cancer model NCI-H2291 led to cellular resistance to the G12C-specific inhibitor AZ'8037 due to continuing active MAPK and PI3K cascades in the presence of the inhibitor. Overall, our study provides a comprehensive assessment of co-occurring KRAS mutations in NSCLC and in vitro evidence of the negative impact of co-occurring KRAS mutations on cellular response to G12C inhibitors, highlighting the need for a comprehensive KRAS tumour genotyping for optimal patient selection for treatment with a KRAS G12C inhibitor.
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