19th March 2019

Breast cancer is a highly heterogeneous tumour conventionally classified into four molecular subtypes, i.e., Luminal A, Luminal B, HER2-enriched, and triple-negative breast cancer. In clinical practice precise molecular subtyping is a powerful approach for fast and efficient treatment and facilitates the delivery of personalised medicine approach. Immunohistochemistry (IHC) is the standard approach but the antibodies used can be highly heterogeneous, costly, and unstable.  Molecular imaging can be a better approach but due to scarcity of specific probes the development of novel and highly specific molecular probes for precisely differentiating breast cancer molecular subtypes is needed.  Using cell based selections improves the chances of aptamers binding to live cells over traditional protein or peptide targets.

In this study a Cell-SELEX method was used with SK-BR-3 breast cancer cells as the target cell, while MCF-7 and MDA-MB-231 breast cancer cells and MCF-10A human normal mammary epithelial cells were utilised as negative control cells. Six ssDNA aptamer probes capable of specifically binding to SK-BR-3 breast cancer cells were identified and aptamer sk6 exhibited both the best specificity and the highest binding affinity among the six aptamer candidates. Aptamer sk6 was subsequently truncated and optimised and a new aptamer probe, sk6Ea, composed of only 53 nt and exhibiting similar recognition ability to that of sk6, was obtained. In flow cytometry, confocal microscopy and in vivo tumour imaging the aptamer sk6Ea had higher specificity against SK-BR-3 breast cancer cells and could not only distinguish breast cancer molecular subtypes both in vitro and in vivo but also differentiate SK-BR-3 breast cancer cells from other cancer cells and normal cells.

Although the aptamer sk6Ea has potential there are still some challenges to be addressed.  While aptamer sk6Ea can distinguish HER2-enriched breast cancer cells from three other breast cancer subtypes and adjacent normal breast tissues (ANBTs), it lacked the ability in to further differentiate among Luminal A, Luminal B, and triple-negative breast cancer tissues. To achieve this purpose, it was suggested that additional non specific blocking methods be introduced and additional breast cancer molecular subtype-specific aptamers should be developed, as well as additional biomarkers, creating an even more specific multiplex assay approach for IHC application.

Aptamer Group has also successfully selected cell based biomarkers with additional cell lines included for specificity (see our throat cancer biomarker selection data https://www.aptamergroup.co.uk/cell-imaging-aptamers-can-monitor-the-different-stages-of-cancer/ ), and also delivers minimal fragment Optimers™ for improved binding over standard aptamers. Modified bases can also be included if desired for stability.  If you would like more information on aptamers for your research contact us using the form below.

References:

Liu, M., Wang, Z., Tan, T., Chen, Z., Mou, X., Yu, X., Deng, Y., Lu, G., He, N. (2018).  An Aptamer-Based Probe for Molecular Subtyping of Breast Cancer. Theranostics. 2018; 8(20): 5772–5783.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276286/

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