ArticlePloS one2018
Acquired resistance to AZD9291 as an upfront treatment is dependent on ERK signaling in a preclinical model.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- The roles of MASPIN expression and subcellular localization in non-small cell lung cancer.Bioscience reports · 2020Pooled it
- A combined strategy of EGFR-MET bispecific antibody and HER3 ADC to overcome osimertinib resistance in NSCLC.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- SOS1 inhibition suppresses the emergence of osimertinib resistance to generate a durable response inScience signaling · 2025Article
- The Role of Proteomics and Phosphoproteomics in the Discovery of Therapeutic Targets and Biomarkers in Acquired EGFR-TKI-Resistant Non-Small Cell Lung Cancer.International journal of molecular sciences · 2023Review
- Cytoplasmic expression of G protein-coupled estrogen receptor 1 correlates with poor postoperative prognosis in non-small cell lung cancer.Journal of thoracic disease · 2022Article
- ERK inhibitor ASN007 effectively overcomes acquired resistance to EGFR inhibitor in non-small cell lung cancer.Investigational new drugs · 2022Article
- Preclinical Models for Acquired Resistance to Third-Generation EGFR Inhibitors in NSCLC: Functional Studies and Drug Combinations Used to Overcome Resistance.Frontiers in oncology · 2022Review
- Review
- Review
- Managing Acquired Resistance to Third-Generation EGFR Tyrosine Kinase Inhibitors Through Co-Targeting MEK/ERK Signaling.Lung Cancer (Auckland, N.Z.) · 2021Review
- Article
- Role of liquid biopsy in oncogene-addicted non-small cell lung cancer.Translational lung cancer research · 2019Review
- Acquired BRAF G469A Mutation as a Resistance Mechanism to First-Line Osimertinib Treatment in NSCLC Cell Lines Harboring an EGFR Exon 19 Deletion.Targeted oncology · 2019Article
- Liquid Biopsy for the Detection of Resistance Mechanisms in NSCLC: Comparison of Different Blood Biomarkers.Journal of clinical medicine · 2019Review
- Review
- Comprehensive analysis of circular RNA profiling in AZD9291-resistant non-small cell lung cancer cell lines.Thoracic cancer · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
AZD9291 (osimertinib) is approved for standard care in patients with EGFR T790M-positive non-small cell lung cancer (NSCLC) after prior EGFR TKI progression. Furthermore, AZD9291 is now being evaluated as a first-line treatment for NSCLC patients with activation EGFR mutations. Based on previous experiments, resistance to AZD9291 as a first-line treatment may also emerge. Thus, identification and understanding of resistance mechanisms to AZD9291 as a first-line treatment can help direct development of future therapies. AZD9291-resistant cells (PC9/AZDR) were established using EGFR inhibitor-naïve PC9 cells. Resistance mechanisms were analyzed using next-generation sequencing (NGS) and a proteome profiler array. Resistance to AZD9291 developed through aberrant activation of ERK signaling by an EGFR-independent mechanism. The combination of a MEK inhibitor with AZD9291 restored the sensitivity of PC9/AZDR cells in vitro and in vivo. PC9/AZDR cells also showed increased MET expression and an HRAS G13R mutation. In addition, maspin expression was higher after AZD9291 treatment in PC9/AZDR cells. Sustained ERK activation confers resistance to AZD9291 as a first-line therapy. Thus, co-targeting EGFR and MEK may be an effective strategy to overcome resistance to AZD9291.
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