Exosomes and breast cancer drug resistance

Abstract

Drug resistance is a daunting challenge in the treatment of breast cancer (BC). Exosomes, as intercellular communicative vectors in the tumor microenvironment, play an important role in BC progression. With the in-depth understanding of tumor heterogeneity, an emerging role of exosomes in drug resistance has attracted extensive attention. The functional proteins or non-coding RNAs contained in exosomes secreted from tumor and stromal cells mediate drug resistance by regulating drug efflux and metabolism, pro-survival signaling, epithelial–mesenchymal transition, stem-like property, and tumor microenvironmental remodeling. In this review, we summarize the underlying associations between exosomes and drug resistance of BC and discuss the unique biogenesis of exosomes, the change of exosome cargo, and the pattern of release by BC cells in response to drug treatment. Moreover, we propose exosome as a candidate biomarker in predicting and monitoring the therapeutic drug response of BC and as a potential target or carrier to reverse the drug resistance of BC.

Communication Between Epithelial–Mesenchymal Plasticity and Cancer Stem Cells: New Insights Into Cancer Progression

“…EMT has been associated with cancer stemness, characterized by an increase in the number of cancer stem cells (CSCs) (13)(14)(15)(16). CSCs are subclone cells in the tumor tissue that obtain stem cell traits (17,18).…”

Circulating extracellular vesicles are effective biomarkers for predicting response to cancer therapy

“…[13,17]. It has been demonstrated that EVs are involved in resistance mechanisms [32] and may induce immune escape by releasing proapoptotic molecules [33]. Another study by Federici et al has also illustrated that low pH-induced reduction of antitumor drug uptake and increased release of EVs with an antitumor drug are important mechanisms for the occurrence of drug resistance [34].…”

The Emerging Role of Extracellular Vesicles in Endocrine Resistant Breast Cancer

“…Breast tumor-derived EVs have been reported to have a role in all cancer hallmarks controlling a wide range of pathways and regulating gene expression by transferring their intra-vesicular content (proteins, lipids, enzymes, metabolites, DNA, mRNA, miRNA, long and short non-coding RNA) into recipient cells [ 40 ]. In addition to regulating invasion, vessel formation, pre-metastatic niche preparation, and immune surveillance escape, the bioactive molecules carried by EVs have been proposed as important players in the mechanisms of resistance to therapeutic treatments [ 41 , 42 ] and might represent promising candidate biomarkers for breast cancers [ 43 , 44 ].…”