ArticleEBioMedicine2019
An integrative pharmacogenomics analysis identifies therapeutic targets in KRAS-mutant lung cancer.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- A systematic review of genetic ancestry as a risk factor for incidence of non-small cell lung cancer in the US.Frontiers in genetics · 2023Pooled it
- Establishment and validation of a novel anoikis-related prognostic signature of lung squamous cell carcinoma.Translational cancer research · 2026Article
- Mutant and Wild-Type RAS Cross-talk and Stoichiometric Deficiencies Are Determinants of Sensitivity to Targeted Therapies in KRASG12R Pancreatic Ductal Adenocarcinoma.Cancer research · 2026Article
- Dependency of Non-Small Cell Lung Cancer Cells on Glutamine and Glucose Levels in the Presence of Metformin.The Eurasian journal of medicine · 2026Article
- Review
- Improving synergistic drug combination prediction with signature-based gene expression features in oncology.Frontiers in pharmacology · 2025Article
- Identification of potential diagnostic targets and therapeutic strategies for anoikis-related biomarkers in lung squamous cell carcinoma using machine learning and computational virtual screening.Frontiers in pharmacology · 2025Article
- Targeted degradation of Pin1 by protein-destabilizing compounds.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Gene signatures of endoplasmic reticulum stress and mitophagy for prognostic risk prediction in lung adenocarcinoma.IET systems biology · 2024Article
- Analysis of Methylome of Different Forms of Basal Cell Hyperplasia and Squamous Cell Metaplasia of Bronchial Epithelium.Bulletin of experimental biology and medicine · 2024Article
- Natural products targeting the MAPK-signaling pathway in cancer: overview.Journal of cancer research and clinical oncology · 2024Review
- Identification of High-Risk Single Nucleotide Polymorphisms in the Human CYB5R3 Gene Responsible for Recessive Congenital Methemoglobinemia: A Computational Approach.Molecular syndromology · 2023Article
- lncSNHG3 drives breast cancer progression by epigenetically increasing CSNK2A1 expression level.Aging · 2023Article
- CircNDST1 promotes papillary thyroid cancer progression via its interaction with CSNK2A1 to activate the PI3K-Akt pathway and epithelial-mesenchymal transition.Journal of endocrinological investigation · 2023Article
- Comprehensive analysis of mitophagy-related genes in NSCLC diagnosis and immune scenery: based on bulk and single-cell RNA sequencing data.Frontiers in immunology · 2023Article
- Long noncoding RNA LINC01426 promotes the progression of lung adenocarcinoma via regulating miRNA-125a-5p/ casein kinase 2 alpha 1 axis.Bioengineered · 2022Article
- Non-genetic adaptive resistance to KRASFrontiers in oncology · 2022Review
- The Genetic Changes of Hepatoblastoma.Frontiers in oncology · 2021Review
- c-Myc Upregulated by High Glucose Inhibits HaCaT Differentiation by S100A6 Transcriptional Activation.Frontiers in endocrinology · 2021Article
- Druggable driver gene alterations in redefined large cell carcinoma in Chinese patients: an observational study.Translational cancer research · 2020Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundKRAS mutations are the most frequent oncogenic aberration in lung adenocarcinoma. KRAS mutant isoforms differentially shape tumour biology and influence drug responses. This heterogeneity challenges the development of effective therapies for patients with KRAS-driven non-small cell lung cancer (NSCLC).
methodsWe developed an integrative pharmacogenomics analysis to identify potential drug targets to overcome MEK/ERK inhibitor resistance in lung cancer cell lines with KRAS(G12C) mutation (n = 12). We validated our predictive in silico results with in vitro models using gene knockdown, pharmacological target inhibition and reporter assays.
findingsOur computational analysis identifies casein kinase 2A1 (CSNK2A1) as a mediator of MEK/ERK inhibitor resistance in KRAS(G12C) mutant lung cancer cells. CSNK2A1 knockdown reduces cell proliferation, inhibits Wnt/β-catenin signalling and increases the anti-proliferative effect of MEK inhibition selectively in KRAS(G12C) mutant lung cancer cells. The specific CK2-inhibitor silmitasertib phenocopies the CSNK2A1 knockdown effect and sensitizes KRAS(G12C) mutant cells to MEK inhibition.
interpretationOur study supports the importance of accurate patient stratification and rational drug combinations to gain benefit from MEK inhibition in patients with KRAS mutant NSCLC. We develop a genotype-based strategy that identifies CK2 as a promising co-target in KRAS(G12C) mutant NSCLC by using available pharmacogenomics gene expression datasets. This approach is applicable to other oncogene driven cancers. FUND: This work was supported by grants from the National Natural Science Foundation of China, the National Key Research and Development Program of China, the Lung Cancer Research Foundation and a Mildred-Scheel postdoctoral fellowship from the German Cancer Aid Foundation.
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