Extracellular vesicles in the treatment and diagnosis of breast cancer: a status update

Abstract

Breast cancer is one of the leading causes of cancer-related death in women. Currently, the treatment of breast cancer is limited by the lack of effectively targeted therapy and patients often suffer from higher severity, metastasis, and resistance. Extracellular vesicles (EVs) consist of lipid bilayers that encapsulate a complex cargo, including proteins, nucleic acids, and metabolites. These bioactive cargoes have been found to play crucial roles in breast cancer initiation and progression. Moreover, EV cargoes play pivotal roles in converting mammary cells to carcinogenic cells and metastatic foci by extensively inducing proliferation, angiogenesis, pre-metastatic niche formation, migration, and chemoresistance. The present update review mainly discusses EVs cargoes released from breast cancer cells and tumor-derived EVs in the breast cancer microenvironment, focusing on proliferation, metastasis, chemoresistance, and their clinical potential as effective biomarkers.

Cell Type-Specific Extracellular Vesicles and Their Impact on Health and Disease

“…Some of the biomarkers found in EVs include miR-1246 (breast cancer), PSA (prostate cancer), and upregulated lncRNA (liver cancer) [ 85 ]. EVs that are known to target cancer can be modified to incorporate strategies to combat cancer [ 94 ]. For example, lung cancer cell-derived EVs can be loaded with an oncolytic adenovirus combined with chemotherapeutic drugs [ 95 ].…”

“…Connexin-46 (Cx-46), a protein that is important for gap junction channels [ 98 ], is shown to be present in high concentrations in inflammatory breast cancer (IBC)-derived EVs [ 99 ]. Inflammatory carcinoma of the breast is an often missed diagnosis and is confused with mastitis, so having a liquid biopsy-based cancer detection could be transformational [ 94 , 100 ]. To detect whether breast cancer is estrogen receptor-based or not, 241 unique serum-derived EV (sEV) proteins were profiled [ 93 ].…”

Extracellular Vesicles in Breast Cancer: From Intercellular Communication to Therapeutic Opportunities

“…Exosomal miRNAs, including miR-423-5p and miR-9-5p, contribute to resistance against cisplatin and tamoxifen, respectively. Notably, EVs carrying miR-378a-3p and miR-378d activate Wnt and Notch pathways, fostering a drug-resistant phenotype [123]. Meanwhile, development of resistance to radiotherapy due to expression of transforming growth factor-β1 (TGF-β1) is implicated as an endogenous factor, particularly when secreted in an EV-associated form (TGF-β1EV) within radiated tumours which eventually enhanced infiltration of Tregs and phosphorylation of protein kinase C zeta (PKC-ζ) in breast tumour tissue [124].…”