ArticleCancer discovery2013
Coordinate direct input of both KRAS and IGF1 receptor to activation of PI3 kinase in KRAS-mutant lung cancer.
Article in Cancer discovery, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed, 163 citations in OpenAlex.
- Elevated FBXL6 activates both wild-type KRAS and mutant KRASMilitary Medical Research · 2023Trial
- KRAS mutated lung adenocarcinoma responds to pan-ERBB and Aurora kinase inhibitors.NPJ precision oncology · 2026Article
- The complex journey of targeting RAS in oncology.BMC cancer · 2025Review
- Progress of KRAS G12C inhibitors in the treatment of refractory colorectal cancer and strategies for drug resistance response.Investigational new drugs · 2025Review
- Copper-enriched automotive brake wear particles perturb human alveolar cellular homeostasis.Particle and fibre toxicology · 2025Article
- ASAP1 and ARF1 Regulate Myogenic Differentiation in Rhabdomyosarcoma by Modulating TAZ Activity.Molecular cancer research : MCR · 2025Article
- Towards Targeting Endothelial Rap1B to Overcome Vascular Immunosuppression in Cancer.International journal of molecular sciences · 2024Review
- Preclinical Therapeutic Efficacy of RAF/MEK/ERK and IGF1R/AKT/mTOR Inhibition in Neuroblastoma.Cancers · 2024Article
- LKB1 depletion-mediated epithelial-mesenchymal transition induces fibroblast activation in lung fibrosis.Genes & diseases · 2024Article
- Cost and time-efficient construction of a 3'-end mRNA library from unpurified bulk RNA in a single tube.Experimental & molecular medicine · 2024Article
- Mediating kinase activity in Ras-mutant cancer: potential for an individualised approach?Frontiers in pharmacology · 2024Review
- Signature-driven repurposing of Midostaurin for combination with MEK1/2 and KRASG12C inhibitors in lung cancer.Nature communications · 2023Article
- Oncogenic Ras deregulates cell-substrate interactions during mitotic rounding and respreading to alter cell division orientation.Current biology : CB · 2023Article
- ADAMTS9-AS1 Long Non‑coding RNA Sponges miR‑128 and miR-150 to Regulate Ras/MAPK Signaling Pathway in Glioma.Cellular and molecular neurobiology · 2023Article
- Long non-coding RNA HIF1A-As2 and MYC form a double-positive feedback loop to promote cell proliferation and metastasis in KRAS-driven non-small cell lung cancer.Cell death and differentiation · 2023Article
- The Combination of Trametinib and Ganitumab is Effective in RAS-Mutated PAX-Fusion Negative Rhabdomyosarcoma Models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Targeting RAS mutants in malignancies: successes, failures, and reasons for hope.Cancer communications (London, England) · 2023Review
- Article
- NT157 exerts antineoplastic activity by targeting JNK and AXL signaling in lung cancer cells.Scientific reports · 2022Article
- Mini Review: Molecular Interpretation of the IGF/IGF-1R Axis in Cancer Treatment and Stem Cells-Based Therapy in Regenerative Medicine.International journal of molecular sciences · 2022Review
39 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
unlabelledUsing a panel of non-small cell lung cancer (NSCLC) lines, we show here that MAP-ERK kinase (MEK) and RAF inhibitors are selectively toxic for the KRAS-mutant genotype, whereas phosphoinositide 3-kinase (PI3K), AKT, and mTOR inhibitors are not. IGF1 receptor (IGF1R) tyrosine kinase inhibitors also show selectivity for KRAS-mutant lung cancer lines. Combinations of IGF1R and MEK inhibitors resulted in strengthened inhibition of KRAS-mutant lines and also showed improved effectiveness in autochthonous mouse models of Kras-induced NSCLC. PI3K pathway activity is dependent on basal IGF1R activity in KRAS-mutant, but not wild-type, lung cancer cell lines. KRAS is needed for both MEK and PI3K pathway activity in KRAS-mutant, but not wild-type, lung cancer cells, whereas acute activation of KRAS causes stimulation of PI3K dependent upon IGF1R kinase activity. Coordinate direct input of both KRAS and IGF1R is thus required to activate PI3K in KRAS-mutant lung cancer cells. SIGNIFICANCE: It has not yet been possible to target RAS proteins directly, so combined targeting of effect or pathways acting downstream of RAS, including RAF/MEK and PI3K/AKT, has been the most favored approach to the treatment of RAS -mutant cancers. This work sheds light on the ability of RASto activate PI3K through direct interaction, indicating that input is also required from a receptor tyrosinekinase, IGF1R in the case of KRAS -mutant lung cancer. This suggests potential novel combination therapeutic strategies for NSCLC.
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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.