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

Abstract

Cancer remains one of the most challenging diseases, as many patients show limited therapeutic response to treatment. Liquid biopsy is a minimally invasive method that has the advantage of providing real-time disease information with the least damage to cancer patients. Extracellular vesicles (EVs) released by the parental cells and protected by lipid bilayer membrane structure represent an emerging liquid biopsy modality. Apart from promoting cell growth, proliferation, and migration, EVs and their cargos (mainly miRNAs and proteins) are also biomarkers for cancer diagnosis and prognosis. Furthermore, their alterations pre-and post-therapy can guide therapeutic strategy determinations for better-stratified therapy. In this review, we summarize the potential clinical significance of EVs and their cargos in therapeutic response monitoring and prediction in several cancers (mainly lung cancer, prostate cancer, breast cancer, melanoma, lymphoma, glioblastoma, and head and neck squamous cell carcinoma) and discuss the questions that require future investigation.

Circulating extracellular vesicles expressing PD1 and PD-L1 predict response and mediate resistance to checkpoint inhibitors immunotherapy in metastatic melanoma

“…In recent years, liquid biopsies are emerging as a very promising alternative to conventional tissue biopsies for cancer detection, by monitoring tumor progression and response to therapy and tracking tumor evolution. Tumor-derived extracellular vesicles (EVs) arises as an alternative source of biomarkers in liquid biopsies because cancer cells actively produce EVs enriched in cancer-promoting cellular contents, such as immunosuppressive proteins like PD-L1 and PD1, mRNAs and micro-RNAs, which mediate the dysregulation of both the tumour and the protumor immune responses with a consequent establishment of resistance to immunotherapy [ 16 , 45 , 46 ]. The need to identify biomarkers that can allow the selection of MM patients with high probability of response to immunotherapy is imperative and the analysis of the mechanisms involved in determining this lack of response could be of help in identifying other therapeutic strategies that, by blocking this resistance mechanism, can reactivate the immune system.…”

Molecular Characterization of Prostate Cancers in the Precision Medicine Era

“…Finally, extracellular vesicles (EVs), due to their specific loads such as proteins, mRNAs, miRNAs, lncRNAs, and lipids, exert important effects on cell signaling and tumor progression and are emerging as possible markers to monitor PCa progression and metastasis [ 159 , 160 ]. In addition, they are also indicators of therapy response in many cancer types, including PCa [ 161 ]. Proteomic studies performed in PCa cell lines and patients showed that EVs are a source of intracellular proteins and may be useful to improve PCa diagnosis [ 162 ].…”

“…Currently, the major limitation in the use of EVs in clinical practice is the lack of a standardized method for the detection and isolation of EVs, due to their small sizes and low densities. Although many technologies are available, the yield is low, and samples are not pure but contain contaminating proteins and reagents [ 159 , 161 ]. The selection of the isolation method to use is related to the downstream application.…”

Enhancement strategies for mesenchymal stem cells and related therapies

“…A recent clinical trial reported improved oxygenation and reduced cytokine storm in COVID-19 patients treated with EVs derived from BM MSCs [ 118 ]. Implementation of EVs for the treatment of many types of cancer has also shown to be a promising approach [ 119 , 120 ].…”