Exosomes in Genitourinary Cancers: Emerging Mediators of Drug Resistance and Promising Biomarkers

Abstract

Drug resistance presents a major obstacle in the treatment of genitourinary cancers. Exosomes as the medium of intercellular communication serve important biological functions and play essential roles in pathological processes, including drug response. Through the transfer of bioactive cargoes, exosomes can modulate drug resistance via multiple mechanisms. This review attempts to elucidate the mechanisms of exosomal cargoes with reference to tumor drug resistance, their role in genitourinary cancers, and their potential clinical applications as candidate biomarkers in liquid biopsy.

Biological, pathological, and multifaceted therapeutic functions of exosomes to target cancer

“…Due to their high tolerance, highly invasive, long half-life, non-toxic, and non-immunogenic properties, exosomes promote the delivery of various drugs including adriamycin and paclitaxel to treat cancer [179][180][181][182][183]. The capacity of exosomes to identify the cancerous cells and infiltrate them makes drug delivery more efficient and targeted.…”

“…Exosomes have been considered potential vaccines for treating cancer because of their capacity to transport antigens and MHC-peptide complexes and their role in enhancing immune responses [184]. Exosomes generated by dendritic cells (known to be immune system modulators) are most effective in immunotherapy because they trigger an immune response by presenting tumor antigens and enhance the effectiveness of the immune system [183,[186][187][188]. Studies have proved that these exosomes carrying tumor antigens can stimulate CD4+ and CD8+ T cells, producing adaptive immune responses and anti-tumor T cell responses, leading to the shrinkage of the tumor cells [184,185,187].…”

“…Exosomes produced from cells infected with the virus are capable of triggering an antiviral interferon (IFN) response, which promotes the development of vaccines for cancer. Exosomes derived from NK cells are found to produce antitumor effects against aggressive melanoma [181,183]. Modified exosomes that carry Tumor Necrosis Factor (TNF)-related Apoptosis-inducing Ligand (TRAIL) induce apoptosis in cancer cells, thereby decreasing tumor growth [179,182,186].…”

Different origin-derived exosomes and their clinical advantages in cancer therapy

“…Exosomes are important mediators of intercellular communication in the development of drug resistance, and can be used as delivery tools ( 122 , 133 ). They have become a key carrier to deliver miRNA to cancer cells ( 70 , 134 ), and their function is often achieved through pathways related to transforming growth factor-β (TGF-β) ( 135 ).…”

Unraveling the Multifaceted Roles of Extracellular Vesicles: Insights into Biology, Pharmacology, and Pharmaceutical Applications for Drug Delivery

“…In models of Parkinson’s disease, the correlation between increased α-syn concentration and decreased interaction between syntaxin4 and VAMP2 results in decreased EV secretion [ 365 ]. In prostate cancer cells, knockdown of t-SNARE (syntaxin 6) significantly decreased EV production and thus reduced drug resistance conferred by this secretion [ 366 ]. Although most SNARE proteins are cell type-specific, it is clear that VAMP7 and SNAP23 are ubiquitous hubs of the membrane fusion process [ 361 ].…”