Extracellular Vesicles as Mediators of Cancer Disease and as Nanosystems in Theranostic Applications

Abstract

Cancer remains a leading cause of death worldwide despite decades of intense efforts to understand the molecular underpinnings of the disease. To date, much of the focus in research has been on the cancer cells themselves and how they acquire specific traits during disease development and progression. However, these cells are known to secrete large numbers of extracellular vesicles (EVs), which are now becoming recognized as key players in cancer. EVs contain a large number of different molecules, including but not limited to proteins, mRNAs, and miRNAs, and they are actively secreted by many different cell types. In the last two decades, a considerable body of evidence has become available indicating that EVs play a very active role in cell communication. Cancer cells are heterogeneous, and recent evidence reveals that cancer cell-derived EV cargos can change the behavior of target cells. For instance, more aggressive cancer cells can transfer their “traits” to less aggressive cancer cells and convert them into more malignant tumor cells or, alternatively, eliminate those cells in a process referred to as “cell competition”. This review discusses how EVs participate in the multistep acquisition of specific traits developed by tumor cells, which are referred to as “the hallmarks of cancer” defined by Hanahan and Weinberg. Moreover, as will be discussed, EVs play an important role in drug resistance, and these more recent advances may explain, at least in part, why pharmacological therapies are often ineffective. Finally, we discuss literature proposing the use of EVs for therapeutic and prognostic purposes in cancer.

Validating Cell Surface Proteases as Drug Targets for Cancer Therapy: What Do We Know, and Where Do We Go?

“…EVs are small cell-derived membrane vesicles, produced either through the endosomal pathway, giving rise to exosomes, or after budding of plasma membrane, resulting in microvesicles [243][244][245][246]. EVs obtained from the serum of cancer patients holds promise as diagnostic and prognostic parameters [229,247,248]. EVs influence tumour growth, metastasis, epithelial-to-mesenchymal transition, and drug resistance [229,[247][248][249].…”

“…EVs obtained from the serum of cancer patients holds promise as diagnostic and prognostic parameters [229,247,248]. EVs influence tumour growth, metastasis, epithelial-to-mesenchymal transition, and drug resistance [229,[247][248][249]. Exosomes transfer various molecules from tumour cells to immune cells and neovascular cells, contributing to the escape from immune surveillance and increased angiogenesis, respectively [231,245,246].…”

Functionalized Nanomaterials as Tailored Theranostic Agents in Brain Imaging

“…The remarkable developments in multimodal molecular imaging methods using various functional nanomaterials have led to the translation of many novel materials into the clinic. These nanomaterials are established to confront the crucial problems encountered by diagnostic imaging techniques [ 1 , 2 ]. Theranostic imaging adopting nanomaterials presents significant improvements over the traditional approaches via increasing blood circulation times, enhanced diagnostic specificity, and organ-specific delivery [ 3 ].…”

Exosomes in Cancer Therapy

“…As discussed above, while exosomes have shown utility in the diagnosis, and treatment of various cancers, recent evidence reveals that cancer-cell-derived exosomes can change the behavior of target cells. The review represented by Burgos-Ravanal [14] cussed that exosomes isolated from aggressive cancer cells can transfer their "traits" to less aggressive cancer cells and convert them into more malignant tumor cells. This review further highlights the role of exosomes in drug resistance, and provides a valuable discussion on why pharmacological therapies are often ineffective.…”