ArticleNPJ precision oncology2021
Combined FGFR and Akt pathway inhibition abrogates growth of FGFR1 overexpressing EGFR-TKI-resistant NSCLC cells.
Article in NPJ precision oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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The trial behind it
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Who cites it
31 citing papers in PubMed, 46 citations in OpenAlex.
- The role of FGFR signaling in SCLC and NSCLC: Current insights and therapeutic perspectives.iScience · 2026Review
- Modulating metabolic signatures to mitigate cabozantinib resistance in FLT3-ITD acute myeloid leukemia cell models.Cell death discovery · 2026Article
- Targeting PLK1 potentiates the antitumor efficacy of EGFR-TKIs through inhibiting the JAK1/STAT3 pathway.Cell death & disease · 2026Article
- Saturation mutagenesis identifies activating and resistance-inducing FGFR kinase domain mutations.Nature genetics · 2026Article
- A Multikinase Inhibitor AX-0085 Blocks FGFR1 Activation to Overcomes Osimertinib Resistance in Non-Small Cell Lung Cancer.Biomedicines · 2025Article
- FGFR Aberrations in Solid Tumors: Mechanistic Insights and Clinical Translation of Targeted Therapies.Cancers · 2025Review
- Article
- IFITM3-MET interaction drives osimertinib resistance through AKT pathway activation in EGFR-mutant non-small cell lung cancer.Molecular cancer · 2025Article
- A novel biguanide-derivative promotes NEDD4-mediated FGFR1 ubiquitination through BMI1 to overcome osimertinib resistance in NSCLC.Cancer biology & medicine · 2025Article
- Protein kinase B inhibitors enhance the sensitivity of translocated promoter region-fibroblast growth factor receptor 1 cells to fibroblast growth factor receptor 1 inhibitor-induced apoptosis.The Journal of international medical research · 2025Article
- Aurora kinases signaling in cancer: from molecular perception to targeted therapies.Molecular cancer · 2025Review
- Strategies to Overcome Resistance to Osimertinib in EGFR-Mutated Lung Cancer.International journal of molecular sciences · 2025Review
- Kinome-Focused CRISPR-Cas9 Screens in African Ancestry Patient-Derived Breast Cancer Organoids Identify Essential Kinases and Synergy of EGFR and FGFR1 Inhibition.Cancer research · 2025Article
- Optimizing Osimertinib for NSCLC: Targeting Resistance and Exploring Combination Therapeutics.Cancers · 2025Review
- Oral microbial signatures underlying recurrence via PI3K/AKT/mTOR pathway modulation in oral squamous cell carcinoma.Journal of oral microbiology · 2025Article
- FGFR1 overexpression promotes resistance to PI3K inhibitor alpelisib in luminal breast cancer cells through receptor tyrosine kinase signaling-mediated activation of the estrogen receptor.Cancer drug resistance (Alhambra, Calif.) · 2025Article
- Article
- Graph-Based Spatial Proximity of Super-Resolved Protein-Protein Interactions Predicts Cancer Drug Responses in Single Cells.Cellular and molecular bioengineering · 2024Article
- Mechanisms of resistance to targeted therapy and immunotherapy in non-small cell lung cancer: promising strategies to overcoming challenges.Frontiers in immunology · 2024Review
- FGFR blockade inhibits targeted therapy-tolerant persister in basal FGFR1- and FGF2-high cancers with driver oncogenes.NPJ precision oncology · 2023Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
EGFR tyrosine kinase inhibitor (TKI) resistance in non-small cell lung cancer (NSCLC) patients is inevitable. Identification of resistance mechanisms and corresponding targeting strategies can lead to more successful later-line treatment in many patients. Using spectrometry-based proteomics, we identified increased fibroblast growth factor receptor 1 (FGFR1) expression and Akt activation across erlotinib, gefitinib, and osimertinib EGFR-TKI-resistant cell line models. We show that while combined EGFR-TKI and FGFR inhibition showed some efficacy, simultaneous inhibition of FGFR and Akt or PI3K induced superior synergistic growth inhibition of FGFR1-overexpressing EGFR-TKI-resistant NSCLC cells. This effect was confirmed in vivo. Only dual FGFR and Akt inhibition completely blocked the resistance-mediating signaling pathways downstream of Akt. Further, increased FGFR1 expression was associated with significantly lower PFS in EGFR-TKI-treated NSCLC patients, and increased FGFR1 were demonstrated in a few post- vs. pre-EGFR-TKI treatment clinical biopsies. The superior therapeutic benefit of combining FGFR and Akt inhibitors provide the rationale for clinical trials of this strategy.
Identifiers
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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.