Applications of Extracellular Vesicles in Triple-Negative Breast Cancer

Abstract

Triple-negative breast cancer (TNBC) is the most aggressive and refractory subtype of breast cancer, often occurring in younger patients with poor clinical prognosis. Given the current lack of specific targets for effective intervention, the development of better treatment strategies remains an unmet medical need. Over the last decade, the field of extracellular vesicles (EVs) has grown tremendously, offering immense potential for clinical diagnosis/prognosis and therapeutic applications. While TNBC-EVs have been shown to play an important role in tumorigenesis, chemoresistance and metastasis, they could be repurposed as potential biomarkers for TNBC diagnosis and prognosis. Furthermore, EVs from various cell types can be utilized as nanoscale drug delivery systems (NDDS) for TNBC treatment. Remarkably, EVs generated from specific immune cell subsets have been shown to delay solid tumour growth and reduce tumour burden, suggesting a new immunotherapy approach for TNBC. Intrinsically, EVs can cross the blood–brain barrier (BBB), which holds great potential to treat the brain metastases diagnosed in one third of TNBC patients that remains a substantial clinical challenge. In this review, we present the most recent applications of EVs in TNBC as diagnostic/prognostic biomarkers, nanoscale drug delivery systems and immunotherapeutic agents, as well as discuss the associated challenges and future directions of EVs in cancer immunotherapy.

Exosome-Based Smart Drug Delivery Tool for Cancer Theranostics

“…The molecular contents of exosomes normally reflect those of their parent cells and can therefore be used as biomarkers for pathophysiological complications (such as cancer). ,, Tumor and stromal cells in the TME have been reported to release exosomes, and their molecular signatures play a dynamic role in cancer. , For example, it has been found that TNBC (triple-negative breast cancer) cells with CCL5 on their surfaces, derived from tumor-derived exosomes, alter TME-associated macrophages and develop a metastatic nature, resulting in a TME favorable for carcinogenesis . Researchers suggest that derived cancer stem cells are involved cancer metastesis .…”

“…Exosomes are the most interesting noninvasive diagnostic biomarkers and therapeutics. Their cargo molecules are involved in cellular communication. , The secretion of exosomes from specific cells or tissues is based entirely on the cellular and philological condensation of cells . The exosome leads to biologically active molecules .…”

“…A clinical study NCT04523389 related to colon cancer focuses on the development of diagnostic markers. TNBC TEVs carry multiple molecules that are sources of diagnostic and prognostic biomarkers . Some of the most complicated cancers, such as breast cancer, , lung cancer, , colon cancer, , prostate cancers, , and liver cancers, , and their related exosome biomarkers with clinical importance are discussed in Table .…”

“…The exosome leads to biologically active molecules . The exosomal molecular signature has a complex association with multiple treatment resistance and carcinogenesis . miRNAs associated with TEXs promote EMT (miRNA-21, miRNA-92b, miRNA-130a, miR-149, miRNA-181c, miRNA-200, miRNA-328, miRNA-423-5p, miRNA-602, and miRNA-1246), tumorigenesis, invasion, and metastasis (let-7a miRNA, miRNA-21, miRNA-221/222, and miRNA-42 …”

Analysis of microRNAs in Exosomes of Breast Cancer Patients in Search of Molecular Prognostic Factors in Brain Metastases

“…Exosomes, on the other hand, are defined by a diameter of 30–100 nm [ 11 , 12 ]. It was their small size that brought exosomes into the focus of drug delivery but also of biomarker research [ 13 ]. They are able to transfer proteins and genetic material [ 14 ].…”