Exosomes are extracellular vesicles secreted by most eukaryotic cells and are involved in intercellular communication. Exosomes contribute to the pathophysiological development of cancers by providing specific bioactive molecules that are crucial at different stages of cancer development, suggesting that exosomes have the potential to serve as diagnostic biomarkers and therapeutic targets. The drug resistance phenomenon associated with exosomes is emerging in several types of cancer. Therefore, understanding the mechanisms of exosome-mediated therapeutic resistance to cancer should provide valuable information for precision cancer therapies.
In addition, exosomes are non-immunogenic in nature and have been used as a delivery system for anticancer drugs, since their membrane composition is similar to that of most cells in the body. Exosomes belong to a subpopulation of extracellular vesicles secreted by the dynamic process of multi-step endocytosis and carry diverse functional molecular loads, including proteins, lipids, nucleic acids (DNA, messenger and non-coding RNA) and metabolites to promote intercellular communication. Proteins and non-coding RNA are among the most abundant contents of exosomes; they have biological functions and are selectively packaged in exosomes. Exosomes derived from tumor, stromal, and immune cells contribute to multiple stages of cancer progression as well as resistance to treatment.
In this review, we will analyze the biogenesis of exosomes and their roles in cancer development. Since the specific contents of exosomes originate in their cells of origin, this property allows exosomes to function as valuable biomarkers. We will also analyze the potential use of exosomes as biomarkers or predictors of diagnosis and prognosis for different therapeutic strategies for various types of cancer. In addition, the applications of exosomes as direct therapeutic targets or vehicles designed to drug manufacturing constitutes an important field of study of exosomes.
A better understanding of exosome biology may pave the way for promising clinical applications based on exosomes. In summary, exosomes derived from tumor, stromal, and immune cells contribute to multiple stages of cancer progression, as well as resistance to treatment. Since the specific contents of exosomes come from their cells of origin, this property allows exosomes to function as valuable diagnostic and prognostic biomarkers. In addition, applications of exosomes as direct therapeutic targets or vehicles designed to manufacture drugs may open up new therapeutic avenues.
A better understanding of exosome biology will undoubtedly help pave the way for exosome-based clinical applications. Exosomes are small extracellular vesicles that contain genetic material, proteins, and lipids. They function as powerful signaling molecules between cancer cells and surrounding cells that form the tumor microenvironment (EMT). Exosomes derived from tumor and stromal cells have been linked to all stages of cancer progression and play an important role in resistance to treatment.
In addition, due to their nature as mediators of communication between cells, they are an integral part of resistance to TME-dependent therapy. In this review, we analyze current techniques for isolating and profiling exosomes and their role in EMT interactions and treatment resistance. We also explore the emerging clinical applications of both exosomes as biomarkers, direct therapeutic targets and designed nanocarriers. To fully understand the TME, it is essential to carefully question people exosomes and their burden.
This understanding is a promising avenue for the development of effective clinical applications. MicroRNAs carried by exosomes promote epithelial-mesenchymal transition and metastasis of liver cancer cells. Cancer is one of the leading causes of death worldwide and it is necessary to elucidate the factors responsible for its progression. Since exosomes affect various aspects of cancer cells, they can be isolated from patients' serum and are considered reliable biomarkers for diagnosis and prognosis for cancer patients.
Recently, the CPT1a-siRNA was loaded into the exosomes and a surface modification was performed with IRGD to promote its selectivity towards colon cancer cells. Exosomes derived from mouse type 4T1 breast cancer cells induce the production of proinflammatory cytokines in macrophages through miR-183. MiR-183 is closely related to carcinogenesis, progression, metastasis, and drug resistance due to dynamic interactions with cancer cells. In a clinical trial on colorectal cancer, exosome was used in combination with granulocyte and macrophage colony-stimulating factor as adjunctive therapy and was found to increase the level and function of cytotoxic T lymphocytes in patients. Ongoing clinical efforts include treating patients with cancer (non-small cell lung cancer) with CD-derived exosomes (dexosomes) to activate the anti-tumor immune response (7).
Survivin in breast cancer-derived exosomes activates fibroblasts by up-regulating SOD1, whose feedback promotes cancer proliferation and metastasis).Exosomes derived from malignant ascites from nineteen patients with pancreatic cancer showed a higher expression of CD133, compared to exosomes derived from patients with gastric cancer or liver cirrhosis. While the rate of exosome production and the heterogeneity of cell-derived exosomes under normal physiological conditions can be difficult to determine in vivo, many in vitro studies indicate that virtually all cell types can produce exosomes, that exosomes are heterogeneous, and that heterogeneity can increase in pathological conditions such as cancer. Exosomes derived from human ovarian cancer samples suppressed the expression of T-cell activation signaling components, such as JAK3 and CD3-; in addition, they induced T-cell apoptosis, as indicated by Taylor et al. VEGFR2 expression is mainly seen in endothelial cells, while VEGFR1 is found in macrophages, cancer cells and fibroblasts.
Metastatic brain tumor radiomics as an imaging biomarker predictive of progression-free survival in patients with non-small cell lung cancer with brain metastases receiving tyrosine kinase inhibitors. Some of the contents act as mediators of signal transduction between cancer cells and cancer cells with cancer cells or cancer cells with cells associated with the tumor microenvironment, and contribute to the development, invasion, metastasis and drug resistance of tumors.
