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Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
Published on: November 22, 2021
Targeting non-coding RNAs to overcome osimertinib resistance in EGFR-mutated non-small cell lung cancer
Beilei Zeng1,2, Kelun Gan1, Yuanhang Yu1
1Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China.
Abstract:
Osimertinib, a third-generation inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, exhibits remarkable efficacy in prolonging the survival of patients with non-small cell lung cancer (NSCLC) carrying EGFR mutations, surpassing the efficacy of first- and second-generation EGFR tyrosine kinases. Nevertheless, the emergence of osimertinib resistance is inevitable, necessitating an investigation into the underlying mechanisms. Increasing evidence has revealed that non-coding RNAs (ncRNAs), including microRNAs, long ncRNAs, and circular RNAs, play a significant role in the development and progression of lung cancer. These ncRNAs regulate essential signaling pathways, offering a novel avenue for understanding the fundamental mechanisms of osimertinib resistance. Recent studies have reported the significant impact of ncRNAs on osimertinib resistance, achieved through various mechanisms that modulate treatment sensitivity. We provide a concise overview of the functions and underlying mechanisms of extensively researched ncRNAs in the development of osimertinib resistance and emphasize their potential clinical application in EGFR-mutated NSCLC resistant to osimertinib. Finally, we discuss the obstacles that must be addressed to effectively translate ncRNA-based approaches into clinical practice.
Insights
Osimertinib resistance in non-small cell lung cancer (NSCLC) is driven by non-coding RNAs (ncRNAs). Understanding these ncRNAs offers new strategies for treating EGFR-mutated NSCLC resistant to osimertinib.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Osimertinib, a third-generation EGFR tyrosine kinase inhibitor, improves survival in EGFR-mutated NSCLC.
- Resistance to osimertinib is a significant clinical challenge in NSCLC treatment.
Purpose of the Study:
- To review the role of non-coding RNAs (ncRNAs) in osimertinib resistance mechanisms.
- To highlight the clinical potential of ncRNAs for overcoming osimertinib resistance in EGFR-mutated NSCLC.
Main Methods:
- Literature review of studies investigating ncRNAs and osimertinib resistance.
- Analysis of ncRNA functions in regulating signaling pathways involved in lung cancer progression.
- Synthesis of current understanding of ncRNA mechanisms in modulating treatment sensitivity.
Main Results:
- ncRNAs, including microRNAs, long ncRNAs, and circular RNAs, are implicated in NSCLC development and progression.
- Specific ncRNAs significantly impact osimertinib resistance by altering sensitivity to the drug.
- ncRNAs regulate key signaling pathways contributing to the emergence of drug resistance.
Conclusions:
- ncRNAs represent a promising therapeutic target for overcoming osimertinib resistance in EGFR-mutated NSCLC.
- Further research is needed to translate ncRNA-based strategies into effective clinical practice.
- Understanding ncRNA functions is crucial for developing novel treatment approaches for resistant NSCLC.
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