Abstract

Breast cancer is one of the most commonly occurring cancers in women globally and is the primary cause of cancer mortality in females. BC is highly heterogeneous with various phenotypic expressions. The overexpression of HER2 is responsible for 15–30% of all invasive BC and is strongly associated with malignant behaviours, poor prognosis and decline in overall survival. Molecular imaging offers advantages over conventional imaging modalities, as it provides more sensitive and specific detection of tumours, as these techniques measure the biological and physiological processes at the cellular level to visualise the disease. Early detection and diagnosis of BC is crucial to improving clinical outcomes and prognosis. While HER2-specific antibodies and nanobodies may improve the sensitivity and specificity of molecular imaging, the radioisotope conjugation process may interfere with and may compromise their binding functionalities. Aptamers are single-stranded oligonucleotides capable of targeting biomarkers with remarkable binding specificity and affinity. Aptamers can be functionalised with radioisotopes without compromising target specificity. The attachment of different radioisotopes can determine the aptamer’s functionality in the treatment of HER2(+) BC. Several HER2 aptamers and investigations of them have been described and evaluated in this paper. We also provide recommendations for future studies with HER2 aptamers to target HER2(+) BC.

Highlights

  • Breast cancer (BC) is a leading cause of mortality in women worldwide [1,2,3] and is highly heterogeneous with various phenotypic expressions [4]

  • BC is a highly heterogenous disease, and the overexpression of human epidermal growth factor receptor 2 (HER2) is strongly associated with poorer prognosis

  • Due to a lack of symptoms and the current imaging modalities lacking the appropriate balance of specificity and sensitivity, there are delays in detecting and diagnosing BC at an early stage for curative surgical treatments

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Summary

Introduction

Breast cancer (BC) is a leading cause of mortality in women worldwide [1,2,3] and is highly heterogeneous with various phenotypic expressions [4]. Aptamers are emerging as promising targeting agents and offer advantages over antibodies in cancer research due to their ease of in vitro synthesis; smaller size; low immunogenicity; pH and temperature stability; and functionalising capabilities that do not risk losing binding specificity or affinity to the target [24,25,26]. Due to their high target specificity and tuneable binding affinities, aptamers targeting HER2 are promising agents in nuclear medicine for the early detection and diagnosis of HER2(+) BC [25,26,27,28]

HER2 Breast Cancer
Early Detection Is Critical
Method of Detection
Molecular Imaging
HER2-Targeted Molecular Imaging with Monoclonal Antibodies
HER2-Targeted Molecular Imaging with Nanobodies
Aptamers
Aptamers in Targeted Theranostics
Diagnostic Applications
Therapeutic Applications
HER2 Aptamers
HER2 Aptamers and Nuclear Medicine Imaging
Potential Therapeutic Applications of HER2 Aptamers
Potential for Theranostic Applications
10. Limitations
Findings
11. Conclusions
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