Abstract

Simple SummaryBreast cancer prevalence is a major challenge worldwide due to the lack of early diagnostics and treatment modalities. In this era of technological advancements, researchers are exploring several grey areas in breast cancer research, which may lead to the appropriate point of care, non-invasive and diagnostic aid for early breast cancer detection and management. Exosome-based research, an emerging area, endeavors to locate and elucidate the role of exosomes in breast cancer diagnostics, immune response and clinical outcomes. This review may provide insights on small extracellular vesicles research and their role in breast cancer. Future extensive studies on exosome biology in conjunction with cancer genetics shall undoubtedly open up new vistas in exosome-based diagnostics for early cancer detection and therapeutics.Despite the recent advancements in therapeutics and personalized medicine, breast cancer remains one of the most lethal cancers among women. The prognostic and diagnostic aids mainly include assessment of tumor tissues with conventional methods towards better therapeutic strategies. However, current era of gene-based research may influence the treatment outcome particularly as an adjunct to diagnostics by exploring the role of non-invasive liquid biopsies or circulating markers. The characterization of tumor milieu for physiological fluids has been central to identifying the role of exosomes or small extracellular vesicles (sEVs). These exosomes provide necessary communication between tumor cells in the tumor microenvironment (TME). The manipulation of exosomes in TME may provide promising diagnostic/therapeutic strategies, particularly in triple-negative breast cancer patients. This review has described and highlighted the role of exosomes in breast carcinogenesis and how they could be used or targeted by recent immunotherapeutics to achieve promising intervention strategies.

Highlights

  • Breast cancer, a heterogeneous disease, is a common cause of death in females worldwide [1,2,3]

  • Exosomes derived from TAMs, containing miR-223 promote the invasive potential of breast cancer cells, promoting tumorigenesis [89]

  • Breast cancer exosomes can bind to selective therapeutic antibodies that can lead to treatment failure due to drug adsorption

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Summary

Introduction

A heterogeneous disease, is a common cause of death in females worldwide [1,2,3]. Breast cancer survival rate has improved due to outcomes in the primary molecular sub-classification when administered with targeted therapies such as hormone therapy and HER2-targeted therapy (e.g., trastuzumab) [6]. The current understanding of breast cancer biology has led to significant improvements in diagnostic and prognostic methods and enhanced novel targeted therapies. Studies have recently elucidated the role of a typical vesicular structure of 30–150 nm diameter called exosomes and/or small extracellular vesicles (sEVs), secreted by various immune cells such as dendritic and Chimeric Antigen Receptor T cells (CAR-T) cells to provide robust diagnostics and therapeutic interventions [9,10]. Stem cells, endothelial cells, dendritic cells, B cells, T cells and especially cancer cells were found to secrete exosomes [12], that can play a crucial role in cell signaling communication, in both paracrine and autocrine manner [13]. Exosomes are found amply in pathological and/or physiological fluids, such as breast milk, cerebrospinal fluid, serum, saliva, urine, plasma and ascites [16], making them promising target molecules as cancer cells release more exosomes than non-cancer cells

Exosomes
CTLs Derived Exosomes
Exosomes Derived from CAR-T Cells
Exosomes Derived from Natural Sources
Exosomal Biomarkers in Breast Cancer
Exosomes in Breast Cancer Aggressiveness
Exosomes as Drug Carriers
Exosomes in Multidrug Resistance
Exosomes in Breast Cancer Diagnosis
Exosomes in Immune Response and Immunotherapy
10. Clinical Application of Exosomes
11. Future Prospects
12. Conclusions
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