Tumor‐derived exosomes: Key players in non‐small cell lung cancer metastasis and their implication for targeted therapy

Abstract

Exosomes represent extracellular vesicles of endocytic origin ranging from 30 to 100 nm that are released by most of eukaryotic cells and can be found in body fluids. These vesicles in carrying DNA, RNA, microRNA (miRNA), Long noncoding RNA, proteins, and lipids serve as intercellular communicators. Due to their role in crosstalk between tumor cells and mesenchymal stroma cells, they are vital for tumor growth, progression, and anticancer drug resistance. Lung cancer is a global leading cause of cancer‐related deaths with 5‐year survival rates of about 7% in patients with distant metastasis. Although the implementation of targeted therapy has improved the clinical outcome of nonsmall cell lung cancer, drug resistance remains a major obstacle. Lung tumor‐derived exosomes (TDEs) conveying molecular information from tumor cells to their neighbor cells or cells at distant sites of the body activate the tumor microenvironment (TME) and facilitate tumor metastasis. Exosomal miRNAs are also considered as noninvasive biomarkers for early diagnosis of lung cancer. This review summarizes the influence of lung TDEs on the TME and metastasis. Their involvement in targeted therapy resistance and potential clinical applications are discussed. Additionally, challenges encountered in the development of exosome‐based therapeutic strategies are addressed.

Tumor-Intrinsic PD-L1 Exerts an Oncogenic Function through the Activation of the Wnt/β-Catenin Pathway in Human Non-Small Cell Lung Cancer

“…Recent studies have demonstrated that both cellular and exosomal microRNAs regulate the expression of genes that play essential roles in cancer cell migration, invasion, and metastasis [ 13 , 14 ].…”

Emerging micro-nanotechnologies for extracellular vesicles in immuno-oncology: from target specific isolations to immunomodulation

“…Furthermore, TEV secretion constitutes a large portion of the formation of the tumor microenvironment and drug resistance, especially during excessive stress when the secretion is substantially increased. 37…”

“…177 Additionally, the RNA and miRNA cargo of TEVs play an especially crucial role in antitumor responses and, therefore, remain an important research topic for potential therapeutic intervention. 37 TEVs have been shown to elicit antitumor responses through direct activation of immune cells by transference of certain miRNA during cellular uptake. 178,179 One study reveals how the delivery of tumor derived exosomal miR-130 can direct the polarization of macrophages to inhibit tumor invasion.…”

Molecular Docking and Intracellular Translocation of Extracellular Vesicles for Efficient Drug Delivery

“…Moreover, in lung cancer, gefitinib (Iressa), an anticancer drug that inhibits the epidermal growth factor receptor (EGFR), was shown to increase the intracellular translocation of exosomes, but decrease that of liposomes, which are typically used for drug-delivery systems [ 309 ]. In addition, compared to liposome-encapsulated doxorubicin, exosome-encapsulated doxorubicin results in robustly higher anticancer activity against non-small cell lung cancer [ 310 , 311 ]. Furthermore, degradation of the exosomal membrane proteins further enhanced intracellular migration induced by gefitinib treatment [ 304 ]; thus, exosomal membrane lipids may contribute to the promotion of intracellular translocation during gefitinib treatment.…”