Extracellular vesicles in the tumor microenvironment: Therapeutic resistance, clinical biomarkers, and targeting strategies.

Numerous studies have proved that cell-nonautonomous regulation of neoplastic cells is a distinctive and essential characteristic of tumorigenesis. Two way communications between the tumor and the stroma, or within the tumor significantly influence disease progression and modify treatment responses. In the tumor microenvironment (TME), malignant cells utilize paracrine signaling initiated by adjacent stromal cells to acquire resistance against multiple types of anticancer therapies, wherein extracellular vesicles (EVs) substantially promote such events. EVs are nanoscaled particles enclosed by phospholipid bilayers, and can mediate intercellular communications between cancerous cells and the adjacent microenvironment to accelerate pathological proceeding. Here we review the most recent studies of EV biology and focus on key cell lineages of the TME and their EV cargoes that are biologically active and responsible for cancer resistance, including proteins, RNAs, and other potentially essential components. Since EVs are emerging as novel but critical elements in establishing and maintaining hallmarks of human cancer, timely and insightful understanding of their molecular properties and functional mechanisms would pave the road for clinical diagnosis, prognosis, and effective targeting in the global landscape of precision medicine. Further, we address the potential of EVs as promising biomarkers in cancer clinics and summarize the technical improvements in EV preparation, analysis, and imaging. We highlight the practical issues that should be exercised with caution to guide the development of targeting agents and therapeutic methodologies to minimize cancer resistance driven by EVs, thereby allowing to effectively control the early steps of disease exacerbation.

Han L ，Xu J ，Xu Q ，Zhang B ，Lam EW ，Sun Y ... -  《-》

Landscape of extracellular vesicles in the tumour microenvironment: Interactions with stromal cells and with non-cell components, and impacts on metabolic reprogramming, horizontal transfer of neoplastic traits, and the emergence of therapeutic resistance

Extracellular vesicles (EVs) are increasingly recognised as a pivotal player in cell-cell communication, an attribute of EVs that derives from their ability to transport bioactive cargoes between cells, resulting in complex intercellular signalling mediated by EVs, which occurs under both physiological and pathological conditions. In the context of cancer, recent studies have demonstrated the versatile and crucial roles of EVs in the tumour microenvironment (TME). Here, we revisit EV biology, and focus on EV-mediated interactions between cancer cells and stromal cells, including fibroblasts, immune cells, endothelial cells and neurons. In addition, we focus on recent reports indicating interactions between EVs and non-cell constituents within the TME, including the extracellular matrix. We also review and summarise the intricate cancer-associated network modulated by EVs, which promotes metabolic reprogramming, horizontal transfer of neoplastic traits, and therapeutic resistance in the TME. We aim to provide a comprehensive and updated landscape of EVs in the TME, focusing on oncogenesis, cancer progression and therapeutic resistance, together with our future perspectives on the field.

Zhang DX ，Vu LT ，Ismail NN ，Le MTN ，Grimson A ... -  《-》

Extracellular vesicles in the tumor microenvironment: old stories, but new tales.

Han L ，Lam EW ，Sun Y 《Molecular Cancer》

Extracellular vesicles as biomarkers and therapeutic targets for cancer.

Urabe F ，Kosaka N ，Ito K ，Kimura T ，Egawa S ，Ochiya T ... -  《-》

Tumor-derived extracellular vesicles: Regulators of tumor microenvironment and the enlightenment in tumor therapy.

In recent decades, extracellular vesicles (EVs) have been proven to establish an important bridge of communication between cells or cells and their microenvironment. It is well known that EVs play crucial roles in many human diseases, especially in tumors. Tumor-derived EVs (TEVs) are not only involved in epithelial-mesenchymal transition and extracellular matrix remodeling to promote the invasion and metastasis, but also contribute to the suppression of antitumor immune responses by carrying different inhibitory molecules. In this review, we mainly discuss the effects of TEVs on the remodeling of tumor microenvironment through immune and non-immune associated mechanisms. We summarize the latest studies about utilizing EVs in clinical diagnosis and therapeutic drug delivery as well. In addition, the perspective of tumor therapy by targeting EVs is discussed in this review.

Chen J ，Fei X ，Wang J ，Cai Z ... -  《-》