Diagnostics and Therapeutics in Targeting HER2 Breast Cancer: A Novel Approach

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.

Targeting the COP9 signalosome for cancer therapy

“…HER-2 plays a critical role in the transformation and growth of cancers in many malignancies, and is associated with poor prognosis in human cancers 142,143 . HER-2 enhances Jab1/ CSN5 expression through transcriptional activation in breast cancer 144 .…”

The Protein Landscape of Mucinous Ovarian Cancer: Towards a Theranostic

“…Human epidermal growth factor 2 (HER2, ERBB2) is a tyrosine kinase-type receptor that is localised to the cellular membrane, belonging to the epidermal growth factor receptor (EGFR) family [ 48 , 49 ]. Interestingly, whilst ERBB1 ( HER1 , EGFR ) is rarely amplified in MOC, ERBB2 is amplified in roughly one quarter of all cases [ 1 , 50 ].…”

“…Trials are limited due to the disease’s rarity and thus the difficulty in recruiting suitable patient numbers, let alone stratifying for HER2 overexpression. A theranostic targeting HER2 could be an alternative approach using aptamers (nucleotide-based oligomers with targeting capacity) [ 49 ]. Moreover, the HER2-targeting nanobody [ 177 Lu]Lu-DPTA-2Rs15d demonstrated adequate tumour imaging and reduction in murine HER2+ models [ 49 , 54 ].…”

“…A theranostic targeting HER2 could be an alternative approach using aptamers (nucleotide-based oligomers with targeting capacity) [ 49 ]. Moreover, the HER2-targeting nanobody [ 177 Lu]Lu-DPTA-2Rs15d demonstrated adequate tumour imaging and reduction in murine HER2+ models [ 49 , 54 ]. As such, the successful chelation of both diagnostic and therapeutic moieties to a target such as a HER2-targeting nanobody or peptide may lead to advances in MOC clinical outcomes but ultimately relies on the recruitment of sufficient patients.…”

Molecular Imaging in Nanomedical Research 2.0

“…Due to their high specificity and adjustable binding affinities, aptamers targeting HER2 are promising agents in nuclear medicine for the early detection, diagnosis and potential treatment of HER2-positive breast cancer. In their review, Vi and co-workers [ 8 ] describe several HER2 aptamers and discuss their possible translation into clinical practice as novel primary treatments, or as adjuvant therapies for HER2-positive breast cancer.…”