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Long Non-Coding RNAs in HER2-Positive Breast Cancer: From Resistance Mechanisms to Translational Potential.
Thanh Hoa Vo1,2, Edel McNeela1,2, Orla O'Donnovan1,2
1Department of Science, South East Technological University, Waterford, Ireland.
Oncology Research
|June 1, 2026
Summary
Long non-coding RNAs (lncRNAs) are key regulators of drug resistance in HER2-positive breast cancer. Understanding lncRNA mechanisms and translational potential offers new strategies for overcoming therapy evasion.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- HER2-positive breast cancer presents significant challenges due to intrinsic and acquired resistance to targeted therapies.
- Long non-coding RNAs (lncRNAs) are increasingly recognized as crucial regulators in cancer, including drug resistance.
- Specific investigations into lncRNA roles in HER2-positive breast cancer resistance are limited.
Purpose of the Study:
- To synthesize current evidence on lncRNA-mediated resistance mechanisms in HER2-positive breast cancer.
- To highlight the translational potential of lncRNAs as biomarkers and therapeutic targets.
- To provide a roadmap for advancing the clinical utility of lncRNAs in this disease.
Main Methods:
- Review of current literature on lncRNAs and drug resistance in HER2-positive breast cancer.
- Analysis of epigenetic, transcriptional, and post-transcriptional regulatory mechanisms.
- Emphasis on specific lncRNAs (HOTAIR, LINC00969, GAS5) and their roles.
Main Results:
- lncRNAs modulate signaling pathways, microRNA interactions, and the tumor microenvironment to drive resistance.
- ceRNA networks, RNA-binding protein interactions, and exosome-mediated communication are key mechanisms.
- Specific lncRNAs like HOTAIR, LINC00969, and GAS5 exemplify diverse resistance strategies.
Conclusions:
- lncRNAs are promising, yet underexplored, contributors to HER2-positive breast cancer drug resistance.
- Translational opportunities include lncRNAs as liquid-biopsy biomarkers and therapeutic targets (e.g., antisense oligonucleotides, CRISPR-Cas13).
- Integrating exosomal lncRNA profiling with ctDNA monitoring may enable earlier resistance detection and adaptive treatment strategies.
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