Tumor-associated exosomes in cancer progression and therapeutic targets

Abstract

Exosomes are small membrane vesicles that are released by cells into the extracellular environment. Tumor-associated exosomes (TAEs) are extracellular vesicles that play a significant role in cancer progression by mediating intercellular communication and contributing to various hallmarks of cancer. These vesicles carry a cargo of proteins, lipids, nucleic acids, and other biomolecules that can be transferred to recipient cells, modifying their behavior and promoting tumor growth, angiogenesis, immune modulation, and drug resistance. Several potential therapeutic targets within the TAEs cargo have been identified, including oncogenic proteins, miRNAs, tumor-associated antigens, immune checkpoint proteins, drug resistance proteins, and tissue factor. In this review, we will systematically summarize the biogenesis, composition, and function of TAEs in cancer progression and highlight potential therapeutic targets. Considering the complexity of exosome-mediated signaling and the pleiotropic effects of exosome cargoes has challenge in developing effective therapeutic strategies. Further research is needed to fully understand the role of TAEs in cancer and to develop effective therapies that target them. In particular, the development of strategies to block TAEs release, target TAEs cargo, inhibit TAEs uptake, and modulate TAEs content could provide novel approaches to cancer treatment.

Keywords

cancer progression / regulation / therapeutic targets / tumor-associated exosomes

References

[1] Jokhadze N, Das A, Dizon DS. Global cancer statistics: a healthy population relies on population health. CA Cancer J Clin. 2024; 74(3): 224-226.

[2] Thai AA, Solomon BJ, Sequist LV, Gainor JF, Heist RS. Lung cancer. Lancet. 2021; 398(10299): 535-554.

[3] Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024; 74(1): 12-49.

[4] Siegel RL, Jemal A, Wender RC, Gansler T, Ma J, Brawley OW. An assessment of progress in cancer control. CA Cancer J Clin. 2018; 68(5): 329-339.

[5] Jiang J, Mei J, Ma Y, et al. Tumor hijacks macrophages and microbiota through extracellular vesicles. Exploration. 2022; 2(1).

[6] Li W, Liu JB, Hou LK, et al. Liquid biopsy in lung cancer: significance in diagnostics, prediction, and treatment monitoring. Mol Cancer. 2022; 21(1): 25.

[7] Calvo-Lozano O, Garcia-Aparicio P, Raduly LZ, et al. One-step and real-time detection of microRNA-21 in human samples for lung cancer biosensing diagnosis. Anal Chem. 2022; 94(42): 14659-14665.

[8] Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020; 367(6478): eaau6977.

[9] Gurunathan S, Kang MH, Kim JH. A comprehensive review on factors influences biogenesis, functions, therapeutic and clinical implications of exosomes. Int J Nanomed. 2021; 16: 1281-1312.

[10] Chen R, Xu X, Qian Z, et al. The biological functions and clinical applications of exosomes in lung cancer. Cell Mol Life Sci. 2019; 76(23): 4613-4633.

[11] Vanni I, Alama A, Grossi F, Dal Bello MG, Coco S. Exosomes: a new horizon in lung cancer. Drug Discovery Today. 2017; 22(6): 927-936.

[12] Hsu MT, Wang YK, Tseng YJ. Exosomal proteins and lipids as potential biomarkers for lung cancer diagnosis, prognosis, and treatment. Cancers. 2022; 14(3): 732.

[13] Yin L, Liu X, Shao X, et al. The role of exosomes in lung cancer metastasis and clinical applications: an updated review. J Transl Med. 2021; 19(1): 312.

[14] Li MY, Liu LZ, Dong M. Progress on pivotal role and application of exosome in lung cancer carcinogenesis, diagnosis, therapy and prognosis. Mol Cancer. 2021; 20(1): 22.

[15] Zhuang J, Tan J, Wu C, et al. Extracellular vesicles engineered with valency-controlled DNA nanostructures deliver CRISPR/Cas9 system for gene therapy. Nucleic Acids Res. 2020; 48(16): 8870-8882.

[16] Yan H, Bu P. Non-coding RNA in cancer. Essays Biochem. 2021; 65(4): 625-639.

[17] Panni S, Lovering RC, Porras P, Orchard S. Non-coding RNA regulatory networks. Biochim Biophys Acta Gene Regul Mech. 2020; 1863(6): 194417.

[18] Anastasiadou E, Jacob LS, Slack FJ. Non-coding RNA networks in cancer. Nat Rev Cancer. 2018; 18(1): 5-18.

[19] Yin X, Yang J, Wang H, et al. Non-coding genome in small cell lung cancer between theoretical view and clinical applications. Semin Cancer Biol. 2022; 86(3): 237-250.

[20] Hermann DM, Xin W, Bahr M, Giebel B, Doeppner TR. Emerging roles of extracellular vesicle-associated non-coding RNAs in hypoxia: insights from cancer, myocardial infarction and ischemic stroke. Theranostics. 2022; 12(13): 5776-5802.

[21] Hu W, Liu C, Bi ZY, et al. Comprehensive landscape of extracellular vesicle-derived RNAs in cancer initiation, progression, metastasis and cancer immunology. Mol Cancer. 2020; 19(1): 102.

[22] Xu K, Zhang C, Du T, et al. Progress of exosomes in the diagnosis and treatment of lung cancer. Biomed Pharmacother. 2021; 134: 111111.

[23] Gulei D, Irimie AI, Cojocneanu-Petric R, Schultze JL. Berindan-Neagoe I. Exosomes-small players, big sound. Bioconjugate Chem. 2018; 29(3): 635-648.

[24] Reese M, Dhayat SA. Small extracellular vesicle non-coding RNAs in pancreatic cancer: molecular mechanisms and clinical implications. J Hematol Oncol. 2021; 14(1): 141.

[25] Zhou L, Lv T, Zhang Q, et al. The biology, function and clinical implications of exosomes in lung cancer. Cancer Lett. 2017; 407: 84-92.

[26] Colombo M, Raposo G, Thery C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol. 2014; 30: 255-289.

[27] Han QF, Li WJ, Hu KS, et al. Exosome biogenesis: machinery, regulation, and therapeutic implications in cancer. Mol Cancer. 2022; 21(1): 207.

[28] Yu D, Li Y, Wang M, et al. Exosomes as a new frontier of cancer liquid biopsy. Mol Cancer. 2022; 21(1): 56.

[29] Lai JJ, Chau ZL, Chen SY, et al. Exosome processing and characterization approaches for research and technology development. Adv Sci. 2022; 9(15): e2103222.

[30] Sadeghi S, Tehrani FR, Tahmasebi S, Shafiee A, Hashemi SM. Exosome engineering in cell therapy and drug delivery. Inflammopharmacology. 2023; 31(1): 145-169.

[31] Zhou Y, Ren H, Dai B, et al. Hepatocellular carcinoma-derived exosomal miRNA-21 contributes to tumor progression by converting hepatocyte stellate cells to cancer-associated fibroblasts. J Exp Clin Cancer Res. 2018; 37(1): 324.

[32] Zhang H, Deng T, Ge S, et al. Exosome circRNA secreted from adipocytes promotes the growth of hepatocellular carcinoma by targeting deubiquitination-related USP7. Oncogene. 2019; 38(15): 2844-2859.

[33] Ye L, Zhang Q, Cheng Y, et al. Tumor-derived exosomal HMGB1 fosters hepatocellular carcinoma immune evasion by promoting TIM-1(+) regulatory B cell expansion. J Immunother Cancer. 2018; 6(1): 145.

[34] Cheng L, Liu J, Liu Q, et al. Exosomes from melatonin treated hepatocellularcarcinoma cells alter the immunosupression status through STAT3 pathway in macrophages. Int J Biol Sci. 2017; 13(6): 723-734.

[35] Nakano T, Chen IH, Wang CC, et al. Circulating exosomal miR-92b: its role for cancer immunoediting and clinical value for prediction of posttransplant hepatocellular carcinoma recurrence. Am J Transplant. 2019; 19(12): 3250-3262.

[36] Zhu M, Zhang N, Ma J, He S. Integration of exosomal miR-106a and mesothelial cells facilitates gastric cancer peritoneal dissemination. Cell Signal. 2022; 91: 110230.

[37] Zhu AK, Shan YQ, Zhang J, Liu XC, Ying RC, Kong WC. Exosomal NNMT from peritoneum lavage fluid promotes peritoneal metastasis in gastric cancer. Kaohsiung J Med Sci. 2021; 37(4): 305-313.

[38] Kimura Y, Ohzawa H, Miyato H, et al. Intraperitoneal transfer of microRNA-29b-containing small extracellular vesicles can suppress peritoneal metastases of gastric cancer. Cancer Sci. 2023; 114(7): 2939-2950.

[39] Qiu S, Xie L, Lu C, et al. Gastric cancer-derived exosomal miR-519a-3p promotes liver metastasis by inducing intrahepatic M2-like macrophage-mediated angiogenesis. J Exp Clin Cancer Res. 2022; 41(1): 296.

[40] Yang J, Zhang X, Cao J, et al. Circular RNA UBE2Q2 promotes malignant progression of gastric cancer by regulating signal transducer and activator of transcription 3-mediated autophagy and glycolysis. Cell Death Dis. 2021; 12(10): 910.

[41] Zhang Z, Sun C, Zheng Y, Gong Y. circFCHO2 promotes gastric cancer progression by activating the JAK1/STAT3 pathway via sponging miR-194-5p. Cell Cycle. 2022; 21(20): 2145-2164.

[42] Zhang C, Luo Y, Cao J, Wang X, Miao Z, Shao G. Exosomal lncRNA FAM225A accelerates esophageal squamous cell carcinoma progression and angiogenesis via sponging miR-206 to upregulate NETO2 and FOXP1 expression. Cancer Med. 2020; 9(22): 8600-8611.

[43] Tian JW, Zhang HJ, Li SY, Guo YL, Chen G, Yu ZL. Tumor cell-derived extracellular vesicles in modulating phenotypes and immune functions of macrophages: mechanisms and therapeutic applications. J Cancer. 2023; 14(8): 1321-1334.

[44] Li Y, Hu J, Wang M, et al. Exosomal circPABPC1 promotes colorectal cancer liver metastases by regulating HMGA2 in the nucleus and BMP4/ADAM19 in the cytoplasm. Cell Death Discov. 2022; 8(1): 335.

[45] Mashouri L, Yousefi H, Aref AR, Ahadi AM, Molaei F, Alahari SK. Exosomes: composition, biogenesis, and mechanisms in cancer metastasis and drug resistance. Mol Cancer. 2019; 18(1): 75.

[46] Tang Y, Cui Y, Li Z, et al. Radiation-induced miR-208a increases the proliferation and radioresistance by targeting p21 in human lung cancer cells. J Exp Clin Cancer Res. 2016; 35: 7.

[47] Fan J, Xu G, Chang Z, Zhu L, Yao J. miR-210 transferred by lung cancer cell-derived exosomes may act as proangiogenic factor in cancer-associated fibroblasts by modulating JAK2/STAT3 pathway. Clin Sci (Colch). 2020; 134(7): 807-825.

[48] You J, Li M, Cao LM, et al. Snail1-dependent cancer-associated fibroblasts induce epithelial-mesenchymal transition in lung cancer cells via exosomes. QJM. 2019; 112(8): 581-590.

[49] Qi Y, Zha W, Zhang W. Exosomal miR-660-5p promotes tumor growth and metastasis in non-small cell lung cancer. J BUON. 2019; 24(2): 599-607.

[50] You X, Guo Y, Liu X, Ma C. [Exosomes derived from LPS-stimulated macrophages promote TGF-beta1-induced epithelial-mesenchymal transition of human type II alveolar epithelial A549 cells]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2019; 35(8): 673-681.

[51] Mathieu M, Nevo N, Jouve M, et al. Specificities of exosome versus small ectosome secretion revealed by live intracellular tracking of CD63 and CD9. Nat Commun. 2021; 12(1): 4389.

[52] Yang Q, Xu J, Gu J, et al. Extracellular vesicles in cancer drug resistance: roles, mechanisms, and implications. Adv Sci. 2022; 9(34): e2201609.

[53] Chen G, Huang AC, Zhang W, et al. Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature. 2018; 560(7718): 382-386.

[54] de Miguel-Perez D, Russo A, Arrieta O, et al. Extracellular vesicle PD-L1 dynamics predict durable response to immune-checkpoint inhibitors and survival in patients with non-small cell lung cancer. J Exp Clin Cancer Res. 2022; 41(1): 186.

[55] Asvapromtada S, Sonoda H, Kinouchi M, et al. Characterization of urinary exosomal release of aquaporin-1 and -2 after renal ischemia-reperfusion in rats. Am J Physiol Ren Physiol. 2018; 314(4): F584-F601.

[56] Wei H, Chen Q, Lin L, et al. Regulation of exosome production and cargo sorting. Int J Biol Sci. 2021; 17(1): 163-177.

[57] Xia X, Wang Y, Qin Y, Zhao S, Zheng JC. Exosome: a novel neurotransmission modulator or non-canonical neurotransmitter? Ageing Res Rev. 2022; 74: 101558.

[58] Mathieu M, Martin-Jaular L, Lavieu G, Thery C. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat Cell Biol. 2019; 21(1): 9-17.

[59] Zeng Z, Li Y, Pan Y, et al. Cancer-derived exosomal miR-25-3p promotes pre-metastatic niche formation by inducing vascular permeability and angiogenesis. Nat Commun. 2018; 9(1): 5395.

[60] Lan J, Sun L, Xu F, et al. M2 macrophage-derived exosomes promote cell migration and invasion in colon cancer. Cancer Res. 2019; 79(1): 146-158.

[61] Chen P, Li Y, Liu R, et al. Non-small cell lung cancer-derived exosomes promote proliferation, phagocytosis, and secretion of microglia via exosomal microRNA in the metastatic microenvironment. Transl Oncol. 2023; 27: 101594.

[62] Fang T, Lv H, Lv G, et al. Tumor-derived exosomal miR-1247-3p induces cancer-associated fibroblast activation to foster lung metastasis of liver cancer. Nat Commun. 2018; 9(1): 191.

[63] Zhang X, Sai B, Wang F, et al. Hypoxic BMSC-derived exosomal miRNAs promote metastasis of lung cancer cells via STAT3-induced EMT. Mol Cancer. 2019; 18(1): 40.

[64] Wang H, Yu L, Huang P, et al. Tumor-associated exosomes are involved in hepatocellular carcinoma tumorigenesis, diagnosis, and treatment. J Clin Transl Hepatol. 2022; 10(3): 496-508.

[65] Wu M, Wang G, Hu W, Yao Y, Yu XF. Emerging roles and therapeutic value of exosomes in cancer metastasis. Mol Cancer. 2019; 18(1): 53.

[66] Cazzoli R, Buttitta F, Di Nicola M, et al. microRNAs derived from circulating exosomes as noninvasive biomarkers for screening and diagnosing lung cancer. J Thorac Oncol. 2013; 8(9): 1156-1162.

[67] Liang M, Chen X, Wang L, et al. Cancer-derived exosomal TRIM59 regulates macrophage NLRP3 inflammasome activation to promote lung cancer progression. J Exp Clin Cancer Res. 2020; 39(1): 176.

[68] Jiang C, Zhang N, Hu X, Wang H. Tumor-associated exosomes promote lung cancer metastasis through multiple mechanisms. Mol Cancer. 2021; 20(1): 117.

[69] Silvestri R, Nicoli V, Gangadharannambiar P, Crea F, Bootman MD. Calcium signalling pathways in prostate cancer initiation and progression. Nat Rev Urol. 2023; 20(9): 524-543.

[70] Dewdney B, Jenkins MR, Best SA, et al. From signalling pathways to targeted therapies: unravelling glioblastoma’s secrets and harnessing two decades of progress. Signal Transduct Target Ther. 2023; 8(1): 400.

[71] Xiao H, Ye X, Vishwakarma V, Preet R, Dixon DA. CRC-derived exosomes containing the RNA binding protein HuR promote lung cell proliferation by stabilizing c-Myc mRNA. Cancer Biol Ther. 2022; 23(1): 139-149.

[72] Deng Y, Liu X, Huang Y, et al. STIM1-regulated exosomal EBV-LMP1 empowers endothelial cells with an aggressive phenotype by activating the Akt/ERK pathway in nasopharyngeal carcinoma. Cell Oncol. 2023; 46(4): 987-1000.

[73] Harada T, Yamamoto H, Kishida S, et al. Wnt5b-associated exosomes promote cancer cell migration and proliferation. Cancer Sci. 2017; 108(1): 42-52.

[74] Huang L, Wang F, Wang X, et al. M2-like macrophage-derived exosomes facilitate metastasis in non-small-cell lung cancer by delivering integrin alphaVbeta3. MedComm. 2023; 4(1): e191.

[75] Mutschelknaus L, Azimzadeh O, Heider T, et al. Radiation alters the cargo of exosomes released from squamous head and neck cancer cells to promote migration of recipient cells. Sci Rep. 2017; 7(1): 12423.

[76] Altorki NK, Markowitz GJ, Gao D, et al. The lung microenvironment: an important regulator of tumour growth and metastasis. Nat Rev Cancer. 2019; 19(1): 9-31.

[77] Wang C, Xu J, Yuan D, et al. Exosomes carrying ALDOA and ALDH3A1 from irradiated lung cancer cells enhance migration and invasion of recipients by accelerating glycolysis. Mol Cell Biochem. 2020; 469(1-2): 77-87.

[78] Becker A, Thakur BK, Weiss JM, Kim HS, Peinado H, Lyden D. Extracellular vesicles in cancer: cell-to-cell mediators of metastasis. Cancer Cell. 2016; 30(6): 836-848.

[79] Li I, Nabet BY. Exosomes in the tumor microenvironment as mediators of cancer therapy resistance. Mol Cancer. 2019; 18(1): 32.

[80] Hashemi M, Khosroshahi EM, Chegini MK, et al. miRNAs and exosomal miRNAs in lung cancer: new emerging players in tumor progression and therapy response. Pathol Res Pract. 2023; 251: 154906.

[81] Conway EM, Pikor LA, Kung SH, et al. Macrophages, inflammation, and lung cancer. Am J Respir Crit Care Med. 2016; 193(2): 116-130.

[82] Mehla K, Singh PK. Metabolic regulation of macrophage polarization in cancer. Trends Cancer. 2019; 5(12): 822-834.

[83] Gambardella V, Castillo J, Tarazona N, et al. The role of tumor-associated macrophages in gastric cancer development and their potential as a therapeutic target. Cancer Treat Rev. 2020; 86: 102015.

[84] Han C, Zhang C, Wang H, Zhao L. Exosome-mediated communication between tumor cells and tumor-associated macrophages: implications for tumor microenvironment. Oncoimmunology. 2021; 10(1): 1887552.

[85] Guo W, Li Y, Pang W, Shen H. Exosomes: a potential therapeutic tool targeting communications between tumor cells and macrophages. Mol Ther. 2020; 28(9): 1953-1964.

[86] Chen Q, Li Y, Gao W, Chen L, Xu W, Zhu X. Exosome-mediated crosstalk between tumor and tumor-associated macrophages. Front Mol Biosci. 2021; 8: 764222.

[87] Zhou X, Hong Y, Liu Y, et al. Intervening in hnRNPA2B1-mediated exosomal transfer of tumor-suppressive miR-184-3p for tumor microenvironment regulation and cancer therapy. J Nanobiotechnol. 2023; 21(1): 422.

[88] Tan S, Yu H, Zhang Z, Liu Y, Lou G. Hypoxic tumour-derived exosomal miR-1225-5p regulates M2 macrophage polarisation via toll-like receptor 2 to promote ovarian cancer progress. Autoimmunity. 2023; 56(1): 2281226.

[89] Zhu L, Yang Y, Li H, et al. Exosomal microRNAs induce tumor-associated macrophages via PPARgamma during tumor progression in SHH medulloblastoma. Cancer Lett. 2022; 535: 215630.

[90] Li M, Xu H, Qi Y, et al. Tumor-derived exosomes deliver the tumor suppressor miR-3591-3p to induce M2 macrophage polarization and promote glioma progression. Oncogene. 2022; 41(41): 4618-4632.

[91] Zhao S, Mi Y, Guan B, et al. Tumor-derived exosomal miR-934 induces macrophage M2 polarization to promote liver metastasis of colorectal cancer. J Hematol Oncol. 2020; 13(1): 156.

[92] Chen J, Zhang K, Zhi Y, et al. Tumor-derived exosomal miR-19b-3p facilitates M2 macrophage polarization and exosomal LINC00273 secretion to promote lung adenocarcinoma metastasis via Hippo pathway. Clin Transl Med. 2021; 11(9): e478.

[93] Xu L, Wang L, Yang R, Li T, Zhu X. Lung adenocarcinoma cell-derived exosomes promote M2 macrophage polarization through transmission of miR-3153 to activate the JNK signaling pathway. Hum Mol Genet. 2023; 32(13): 2162-2176.

[94] Kong W, Zhang L, Chen Y, Yu Z, Zhao Z. Cancer cell-derived exosomal LINC00313 induces M2 macrophage differentiation in non-small cell lung cancer. Clin Transl Oncol. 2022; 24(12): 2395-2408.

[95] He Z, Wang J, Zhu C, et al. Exosome-derived FGD5-AS1 promotes tumor-associated macrophage M2 polarization-mediated pancreatic cancer cell proliferation and metastasis. Cancer Lett. 2022; 548: 215751.

[96] Shen T, Miao S, Zhou Y, et al. Exosomal AP000439.2 from clear cell renal cell carcinoma induces M2 macrophage polarization to promote tumor progression through activation of STAT3. Cell Commun Signal. 2022; 20(1): 152.

[97] Xie S, Li X, Yan J, Yu H, Chen S, Chen K. Knockdown of liver cancer cell-secreted exosomal PSMA5 controls macrophage polarization to restrain cancer progression by blocking JAK2/STAT3 signaling. Immun, Inflamm Disease. 2024; 12(2): e1146.

[98] Ling HY, Yang Z, Wang PJ, et al. Diffuse large B-cell lymphoma-derived exosomes push macrophage polarization toward M2 phenotype via GP130/STAT3 signaling pathway. Chem Biol Interact. 2022; 352: 109779.

[99] Gu L, Feng C, Li M, Hong Z, Di W, Qiu L. Exosomal NOX1 promotes tumor-associated macrophage M2 polarization-mediated cancer progression by stimulating ROS production in cervical cancer: a preliminary study. Eur J Med Res. 2023; 28(1): 323.

[100] Rao X, Zhou X, Wang G, et al. NLRP6 is required for cancer-derived exosome-modified macrophage M2 polarization and promotes metastasis in small cell lung cancer. Cell Death Dis. 2022; 13(10): 891.

[101] Kim H, Park HJ, Chang HW, et al. Exosome-guided direct reprogramming of tumor-associated macrophages from protumorigenic to antitumorigenic to fight cancer. Bioactive Mater. 2023; 25: 527-540.

[102] Xiao M, Zhang J, Chen W, Chen W. M1-like tumor-associated macrophages activated by exosome-transferred THBS1 promote malignant migration in oral squamous cell carcinoma. J Exp Clin Cancer Res. 2018; 37(1): 143.

[103] Malmberg R, Zietse M, Dumoulin DW, et al. Alternative dosing strategies for immune checkpoint inhibitors to improve cost-effectiveness: a special focus on nivolumab and pembrolizumab. Lancet Oncol. 2022; 23(12): e552-e561.

[104] Carlino MS, Larkin J, Long GV. Immune checkpoint inhibitors in melanoma. Lancet. 2021; 398(10304): 1002-1014.

[105] Ramazi S, Daddzadi M, Sahafnejad Z, Allahverdi A. Epigenetic regulation in lung cancer. MedComm. 2023; 4(6): e401.

[106] Ang HL, Mohan CD, Shanmugam MK, et al. Mechanism of epithelial-mesenchymal transition in cancer and its regulation by natural compounds. Med Res Rev. 2023; 43(4): 1141-1200.

[107] Neviani P, Wise PM, Murtadha M, et al. Natural killer-derived exosomal miR-186 inhibits neuroblastoma growth and immune escape mechanisms. Cancer Res. 2019; 79(6): 1151-1164.

[108] Wang T, Zhang H. Exploring the roles and molecular mechanisms of RNA binding proteins in the sorting of noncoding RNAs into exosomes during tumor progression. J Adv Res. 2023.

[109] Yang Q, Zhao S, Shi Z, et al. Chemotherapy-elicited exosomal miR-378a-3p and miR-378d promote breast cancer stemness and chemoresistance via the activation of EZH2/STAT3 signaling. J Exp Clin Cancer Res. 2021; 40(1): 120.

[110] Kim DH, Park H, Choi YJ, et al. Exosomal miR-1260b derived from non-small cell lung cancer promotes tumor metastasis through the inhibition of HIPK2. Cell Death Dis. 2021; 12(8): 747.

[111] Zhang Z, Yin J, Lu C, Wei Y, Zeng A, You Y. Exosomal transfer of long non-coding RNA SBF2-AS1 enhances chemoresistance to temozolomide in glioblastoma. J Exp Clin Cancer Res. 2019; 38(1): 166.

[112] Li T, Tao Z, Zhu Y, et al. Exosomal annexin A6 induces gemcitabine resistance by inhibiting ubiquitination and degradation of EGFR in triple-negative breast cancer. Cell Death Dis. 2021; 12(7): 684.

[113] Gao Z, Han X, Zhu Y, et al. Drug-resistant cancer cell-derived exosomal EphA2 promotes breast cancer metastasis via the EphA2-Ephrin A1 reverse signaling. Cell Death Dis. 2021; 12(5): 414.

[114] Zhang C, Liu X, Jin S, Chen Y, Guo R. Ferroptosis in cancer therapy: a novel approach to reversing drug resistance. Mol Cancer. 2022; 21(1): 47.

[115] Cao Y. Adipocyte and lipid metabolism in cancer drug resistance. J Clin Invest. 2019; 129(8): 3006-3017.

[116] Zhang H, Wang M, He Y, et al. Chemotoxicity-induced exosomal lncFERO regulates ferroptosis and stemness in gastric cancer stem cells. Cell Death Dis. 2021; 12(12): 1116.

[117] Li Z, Meng X, Wu P, et al. Glioblastoma cell-derived lncRNA-containing exosomes induce microglia to produce complement C5, promoting chemotherapy resistance. Cancer Immunol Res. 2021; 9(12): 1383-1399.

[118] Kugeratski FG, Kalluri R. Exosomes as mediators of immune regulation and immunotherapy in cancer. FEBS J. 2021; 288(1): 10-35.

[119] Jena BC, Mandal M. The emerging roles of exosomes in anti-cancer drug resistance and tumor progression: an insight towards tumor-microenvironment interaction. Biochim Biophys Acta Rev Cancer. 2021; 1875(1): 188488.

[120] Zhang L, Yu D. Exosomes in cancer development, metastasis, and immunity. Biochim Biophys Acta Rev Cancer. 2019; 1871(2): 455-468.

[121] Barros FM, Carneiro F, Machado JC, Melo SA. Exosomes and immune response in cancer: friends or foes? Front Immunol. 2018; 9: 730.

[122] Yuan Y, Wang L, Ge D, et al. Exosomal O-GlcNAc transferase from esophageal carcinoma stem cell promotes cancer immunosuppression through up-regulation of PD-1 in CD8(+) T cells. Cancer Lett. 2021; 500: 98-106.

[123] Clayton A, Mitchell JP, Court J, Linnane S, Mason MD, Tabi Z. Human tumor-derived exosomes down-modulate NKG2D expression. J Immunol. 2008; 180(11): 7249-7258.

[124] Ashiru O, Boutet P, Fernandez-Messina L, et al. Natural killer cell cytotoxicity is suppressed by exposure to the human NKG2D ligand MICA*008 that is shed by tumor cells in exosomes. Cancer Res. 2010; 70(2): 481-489.

[125] Lundholm M, Schroder M, Nagaeva O, et al. Prostate tumor-derived exosomes down-regulate NKG2D expression on natural killer cells and CD8+ T cells: mechanism of immune evasion. PLoS One. 2014; 9(9): e108925.

[126] Ham S, Lima LG, Chai EPZ, et al. Breast cancer-derived exosomes alter macrophage polarization via gp130/STAT3 signaling. Front Immunol. 2018; 9: 871.

[127] Djebali S, Davis CA, Merkel A, et al. Landscape of transcription in human cells. Nature. 2012; 489(7414): 101-108.

[128] Fontemaggi G. Non-coding RNA regulatory networks in post-transcriptional regulation of VEGFA in cancer. IUBMB Life. 2023; 75(1): 30-39.

[129] Saw PE, Xu X, Chen J, Song EW. Non-coding RNAs: the new central dogma of cancer biology. Sci China Life Sci. 2021; 64(1): 22-50.

[130] Toden S, Zumwalt TJ, Goel A. Non-coding RNAs and potential therapeutic targeting in cancer. Biochim Biophys Acta Rev Cancer. 2021; 1875(1): 188491.

[131] Mafi A, Keshavarzmotamed A, Hedayati N, et al. Melatonin targeting non-coding RNAs in cancer: focus on mechanisms and potential therapeutic targets. Eur J Pharmacol. 2023; 950: 175755.

[132] Fortunato O, Gasparini P, Boeri M, Sozzi G. Exo-miRNAs as a new tool for liquid biopsy in lung cancer. Cancers. 2019; 11(6): 888.

[133] Cheng L, Sharples RA, Scicluna BJ, Hill AF. Exosomes provide a protective and enriched source of miRNA for biomarker profiling compared to intracellular and cell-free blood. J Extracell Vesicles. 2014; 3: 23743.

[134] Lu TX, Rothenberg ME. MicroRNA. J Allergy Clin Immunol. 2018; 141(4): 1202-1207.

[135] Yang F, Ning Z, Ma L, et al. Exosomal miRNAs and miRNA dysregulation in cancer-associated fibroblasts. Mol Cancer. 2017; 16(1): 148.

[136] Mori MA, Ludwig RG, Garcia-Martin R, Brandao BB, Kahn CR. Extracellular miRNAs: from biomarkers to mediators of physiology and disease. Cell Metab. 2019; 30(4): 656-673.

[137] Zhang C, Xiao X, Chen M, Aldharee H, Chen Y, Long W. Liver kinase B1 restoration promotes exosome secretion and motility of lung cancer cells. Oncol Rep. 2018; 39(1): 376-382.

[138] Jouida A, McCarthy C, Fabre A, Keane MP. Exosomes: a new perspective in EGFR-mutated lung cancer. Cancer Metastasis Rev. 2021; 40(2): 589-601.

[139] Wang N, Guo W, Song X, et al. Tumor-associated exosomal miRNA biomarkers to differentiate metastatic vs. nonmetastatic non-small cell lung cancer. Clin Chem Lab Med. 2020; 58(9): 1535-1545.

[140] Li H, Xia M, Zheng S, et al. Cerebrospinal fluid exosomal microRNAs as biomarkers for diagnosing or monitoring the progression of non-small cell lung cancer with leptomeningeal metastases. Biotechnol Genet Eng Rev. 2023: 1-22.

[141] Liu H, Li PW, Yang WQ, et al. Identification of non-invasive biomarkers for chronic atrophic gastritis from serum exosomal microRNAs. BMC Cancer. 2019; 19(1): 129.

[142] Ravishankar H, Mangani AS, Phoebe Moses GL, et al. Serum exosomal miRNA as biomarkers for retinoblastoma. Exp Eye Res. 2020; 199: 108184.

[143] Chen L, Cao P, Huang C, Wu Q, Chen S, Chen F. Serum exosomal miR-7977 as a novel biomarker for lung adenocarcinoma. J Cell Biochem. 2020; 121(5-6): 3382-3391.

[144] Han Z, Li Y, Zhang J, et al. Tumor-derived circulating exosomal miR-342-5p and miR-574-5p as promising diagnostic biomarkers for early-stage lung adenocarcinoma. Int J Med Sci. 2020; 17(10): 1428-1438.

[145] Wu J, Feng Z, Wang R, et al. Integration of bioinformatics analysis and experimental validation identifies plasma exosomal miR-103b/877-5p/29c-5p as diagnostic biomarkers for early lung adenocarcinoma. Cancer Med. 2022; 11(23): 4411-4421.

[146] Zhang T, Zhang P, Li HX. CAFs-derived exosomal miRNA-130a confers cisplatin resistance of NSCLC cells through PUM2-dependent packaging. Int J Nanomed. 2021; 16: 561-577.

[147] Wu SG, Shih JY. Management of acquired resistance to EGFR TKI-targeted therapy in advanced non-small cell lung cancer. Mol Cancer. 2018; 17(1): 38.

[148] Hisakane K, Seike M, Sugano T, et al. Exosome-derived miR-210 involved in resistance to osimertinib and epithelial-mesenchymal transition in EGFR mutant non-small cell lung cancer cells. Thorac Cancer. 2021; 12(11): 1690-1698.

[149] Zhang Y, Qian K, Liu X, Zhao X, Zhao T, Lu G. Exosomal mir-625-3p derived from hypoxic lung cancer cells facilitates metastasis by targeting SCAI. Mol Biol Rep. 2022; 49(10): 9275-9281.

[150] Mittal V. Epithelial mesenchymal transition in tumor metastasis. Annu Rev Pathol. 2018; 13: 395-412.

[151] Tam WL, Weinberg RA. The epigenetics of epithelial-mesenchymal plasticity in cancer. Nat Med. 2013; 19(11): 1438-1449.

[152] Zhou J, Wang H, Sun Q, et al. miR-224-5p-enriched exosomes promote tumorigenesis by directly targeting androgen receptor in non-small cell lung cancer. Mol Ther Nucleic Acids. 2021; 23: 1217-1228.

[153] He S, Li Z, Yu Y, et al. Exosomal miR-499a-5p promotes cell proliferation, migration and EMT via mTOR signaling pathway in lung adenocarcinoma. Exp Cell Res. 2019; 379(2): 203-213.

[154] Liu XN, Zhang CB, Lin H, et al. microRNA-204 shuttled by mesenchymal stem cell-derived exosomes inhibits the migration and invasion of non-small-cell lung cancer cells via the KLF7/AKT/HIF-1alpha axis. Neoplasma. 2021; 68(4): 719-731.

[155] Shao C, Huang Y, Fu B, et al. Targeting c-Jun in A549 cancer cells exhibits antiangiogenic activity in vitro and in vivo through exosome/miRNA-494-3p/PTEN signal pathway. Front Oncol. 2021; 11: 663183.

[156] Dai J, Su Y, Zhong S, et al. Exosomes: key players in cancer and potential therapeutic strategy. Signal Transduct Target Ther. 2020; 5(1): 145.

[157] Li D, Meng D, Niu R. Exosome-reversed chemoresistance to cisplatin in non-small lung cancer through transferring miR-613. Cancer Manag Res. 2020; 12: 7961-7972.

[158] Liu S, Wang W, Ning Y, et al. Exosome-mediated miR-7-5p delivery enhances the anticancer effect of Everolimus via blocking MNK/eIF4E axis in non-small cell lung cancer. Cell Death Dis. 2022; 13(2): 129.

[159] Jeong K, Yu YJ, You JY, Rhee WJ, Kim JA. Exosome-mediated microRNA-497 delivery for anti-cancer therapy in a microfluidic 3D lung cancer model. Lab Chip. 2020; 20(3): 548-557.

[160] Rupaimoole R, Slack FJ. MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov. 2017; 16(3): 203-222.

[161] Chen SW, Zhu SQ, Pei X, et al. Cancer cell-derived exosomal circUSP7 induces CD8(+) T cell dysfunction and anti-PD1 resistance by regulating the miR-934/SHP2 axis in NSCLC. Mol Cancer. 2021; 20(1): 144.

[162] Tyagi A, Wu SY, Sharma S, et al. Exosomal miR-4466 from nicotine-activated neutrophils promotes tumor cell stemness and metabolism in lung cancer metastasis. Oncogene. 2022; 41(22): 3079-3092.

[163] Zhao S, Mi Y, Guan B, et al. Correction to: tumor-derived exosomal miR-934 induces macrophage M2 polarization to promote liver metastasis of colorectal cancer. J Hematol Oncol. 2021; 14(1): 33.

[164] Zhao Y, Jin LJ, Zhang XY. Exosomal miRNA-205 promotes breast cancer chemoresistance and tumorigenesis through E2F1. Aging. 2021; 13(14): 18498-18514.

[165] Liu X, Lu Y, Xu Y, et al. Exosomal transfer of miR-501 confers doxorubicin resistance and tumorigenesis via targeting of BLID in gastric cancer. Cancer Lett. 2019; 459: 122-134.

[166] Chen T, Liu Y, Chen J, Zheng H, Chen Q, Zhao J. Exosomal miR-3180-3p inhibits proliferation and metastasis of non-small cell lung cancer by downregulating FOXP4. Thoracic Cancer. 2021; 12(3): 372-381.

[167] Song Z, Jia G, Ma P, Cang S. Exosomal miR-4443 promotes cisplatin resistance in non-small cell lung carcinoma by regulating FSP1 m6A modification-mediated ferroptosis. Life Sci. 2021; 276: 119399.

[168] Wu X, Bian B, Lin Z, et al. Identification of exosomal mRNA, lncRNA and circRNA signatures in an osteoarthritis synovial fluid-exosomal study. Exp Cell Res. 2022; 410(1): 112881.

[169] Chen Y, Wu Y, Guo L, et al. Exosomal Lnc NEAT1 from endothelial cells promote bone regeneration by regulating macrophage polarization via DDX3X/NLRP3 axis. J Nanobiotechnol. 2023; 21(1): 98.

[170] Banerjee M, Rajeswari VD. Critical review on the different roles of exosomes in TNBC and exosomal-mediated delivery of microRNA/siRNA/lncRNA and drug targeting signalling pathways in triple-negative breast cancer. Molecules. 2023; 28(4): 1802.

[171] Ni J, Zhang X, Li J, et al. Tumour-derived exosomal lncRNA-SOX2OT promotes bone metastasis of non-small cell lung cancer by targeting the miRNA-194-5p/RAC1 signalling axis in osteoclasts. Cell Death Dis. 2021; 12(7): 662.

[172] Wu D, Deng S, Li L, et al. TGF-beta1-mediated exosomal lnc-MMP2-2 increases blood-brain barrier permeability via the miRNA-1207-5p/EPB41L5 axis to promote non-small cell lung cancer brain metastasis. Cell Death Dis. 2021; 12(8): 721.

[173] Qu X, Liu B, Wang L, et al. Loss of cancer-associated fibroblast-derived exosomal DACT3-AS1 promotes malignant transformation and ferroptosis-mediated oxaliplatin resistance in gastric cancer. Drug Resist Updat. 2023; 68: 100936.

[174] Zhang R, Xia Y, Wang Z, et al. Serum long non coding RNA MALAT-1 protected by exosomes is up-regulated and promotes cell proliferation and migration in non-small cell lung cancer. Biochem Biophys Res Commun. 2017; 490(2): 406-414.

[175] Feng Z, Li K, Qin K, et al. The LINC00623/NAT10 signaling axis promotes pancreatic cancer progression by remodeling ac4C modification of mRNA. J Hematol Oncol. 2022; 15(1): 112.

[176] Han M, Gu Y, Lu P, et al. Exosome-mediated lncRNA AFAP1-AS1 promotes trastuzumab resistance through binding with AUF1 and activating ERBB2 translation. Mol Cancer. 2020; 19(1): 26.

[177] Han M, Gu Y, Lu P, et al. Retraction Note to: exosome-mediated lncRNA AFAP1-AS1 promotes trastuzumab resistance through binding with AUF1 and activating ERBB2 translation. Mol Cancer. 2022; 21(1): 143.

[178] Castellano JJ, Marrades RM, Molins L, et al. Extracellular vesicle lincRNA-p21 expression in tumor-draining pulmonary vein defines prognosis in NSCLC and modulates endothelial cell behavior. Cancers. 2020; 12(3): 734.

[179] Cheng Y, Dai X, Yang T, Zhang N, Liu Z, Jiang Y. Low long noncoding RNA growth arrest-specific transcript 5 expression in the exosomes of lung cancer cells promotes tumor angiogenesis. J Oncol. 2019; 2019: 2476175.

[180] Poulet C, Njock MS, Moermans C, et al. Exosomal long non-coding RNAs in lung diseases. Int J Mol Sci. 2020; 21(10): 3580.

[181] Yang Y, Jiang C, Yang Y, et al. Silencing of LncRNA-HOTAIR decreases drug resistance of non-small cell lung cancer cells by inactivating autophagy via suppressing the phosphorylation of ULK1. Biochem Biophys Res Commun. 2018; 497(4): 1003-1010.

[182] Yu Z, Tang H, Chen S, et al. Exosomal LOC85009 inhibits docetaxel resistance in lung adenocarcinoma through regulating ATG5-induced autophagy. Drug Resist Updat. 2023; 67: 100915.

[183] Zheng H, Chen C, Luo Y, et al. Tumor-derived exosomal BCYRN1 activates WNT5A/VEGF-C/VEGFR3 feedforward loop to drive lymphatic metastasis of bladder cancer. Clin Transl Med. 2021; 11(7): e497.

[184] Chen C, Luo Y, He W, et al. Exosomal long noncoding RNA LNMAT2 promotes lymphatic metastasis in bladder cancer. J Clin Invest. 2020; 130(1): 404-421.

[185] Chen X, Deng R, Su D, et al. Visual genetic typing of glioma using proximity-anchored in situ spectral coding amplification. Exploration. 2023; 3(5).

[186] Wang FW, Cao CH, Han K, et al. APC-activated long noncoding RNA inhibits colorectal carcinoma pathogenesis through reduction of exosome production. J Clin Invest. 2019; 129(2): 727-743.

[187] Lei Y, Guo W, Chen B, Chen L, Gong J, Li W. Tumor-released lncRNA H19 promotes gefitinib resistance via packaging into exosomes in non-small cell lung cancer. Oncol Rep. 2018; 40(6): 3438-3446.

[188] Zhang W, Cai X, Yu J, Lu X, Qian Q, Qian W. [Retracted] Exosome-mediated transfer of lncRNA RP11-838N2.4 promotes erlotinib resistance in non-small cell lung cancer. Int J Oncol. 2023; 62(1): 10.

[189] Wang M, Zhou L, Yu F, Zhang Y, Li P, Wang K. The functional roles of exosomal long non-coding RNAs in cancer. Cell Mol Life Sci. 2019; 76(11): 2059-2076.

[190] Wu DM, Deng SH, Liu T, Han R, Zhang T, Xu Y. TGF-beta-mediated exosomal lnc-MMP2-2 regulates migration and invasion of lung cancer cells to the vasculature by promoting MMP2 expression. Cancer Med. 2018; 7(10): 5118-5129.

[191] Yu G, Jung H, Kang YY, Mok H. Comparative evaluation of cell-and serum-derived exosomes to deliver immune stimulators to lymph nodes. Biomaterials. 2018; 162: 71-81.

[192] Zhang X, Xu Y, Ma L, et al. Essential roles of exosome and circRNA_101093 on ferroptosis desensitization in lung adenocarcinoma. Cancer Commun. 2022; 42(4): 287-313.

[193] Peng L, Cao Y, Hu C. Identification of exosomal circRNA CD226 as a potent driver of nonsmall cell lung cancer through miR-1224-3p/high mobility group AT-hook 2 axis. Anticancer Drugs. 2022; 33(10): 1126-1138.

[194] Yang B, Teng F, Chang L, et al. Tumor-derived exosomal circRNA_102481 contributes to EGFR-TKIs resistance via the miR-30a-5p/ROR1 axis in non-small cell lung cancer. Aging. 2021; 13(9): 13264-13286.

[195] Shao N, Song L, Sun X. Exosomal circ_PIP5K1A regulates the progression of non-small cell lung cancer and cisplatin sensitivity by miR-101/ABCC1 axis. Mol Cell Biochem. 2021; 476(6): 2253-2267.

[196] Kang Y, You J, Gan Y, et al. Serum and serum exosomal circRNAs hsa_circ_0001492, hsa_circ_0001439, and hsa_circ_0000896 as diagnostic biomarkers for lung adenocarcinoma. Front Oncol. 2022; 12: 912246.

[197] Lee YS, Shibata Y, Malhotra A, Dutta A. A novel class of small RNAs: tRNA-derived RNA fragments (tRFs). Genes Dev. 2009; 23(22): 2639-2649.

[198] Fagan SG, Helm M, Prehn JHM. tRNA-derived fragments: a new class of non-coding RNA with key roles in nervous system function and dysfunction. Prog Neurobiol. 2021; 205: 102118.

[199] Zheng B, Song X, Wang L, et al. Plasma exosomal tRNA-derived fragments as diagnostic biomarkers in non-small cell lung cancer. Front Oncol. 2022; 12: 1037523.

[200] Wang W, Zhu L, Li H, et al. Alveolar macrophage-derived exosomal tRF-22-8BWS7K092 activates Hippo signaling pathway to induce ferroptosis in acute lung injury. Int Immunopharmacol. 2022; 107: 108690.

[201] Shan S, Chen J, Sun Y, et al. Functionalized macrophage exosomes with panobinostat and PPM1D-siRNA for diffuse intrinsic pontine gliomas therapy. Adv Sci. 2022; 9(21): e2200353.

[202] Ha D, Yang N, Nadithe V. Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes: current perspectives and future challenges. Acta Pharm Sin B. 2016; 6(4): 287-296.

[203] Wahlgren J, De LKT, Brisslert M, et al. Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes. Nucleic Acids Res. 2012; 40(17): e130.

[204] Didiot MC, Hall LM, Coles AH, et al. Exosome-mediated delivery of hydrophobically modified siRNA for Huntingtin mRNA silencing. Mol Ther. 2016; 24(10): 1836-1847.

[205] Olejarz W, Dominiak A, Zolnierzak A, Kubiak-Tomaszewska G, Lorenc T. Tumor-derived exosomes in immunosuppression and immunotherapy. J Immunol Res. 2020; 2020: 6272498.

[206] Lv B, Wang Y, Ma D, et al. Immunotherapy: reshape the tumor immune microenvironment. Front Immunol. 2022; 13: 844142.

[207] Bai R, Cui J. Development of immunotherapy strategies targeting tumor microenvironment is fiercely ongoing. Front Immunol. 2022; 13: 890166.

[208] Yang F, Wang T, Du P, Fan H, Dong X, Guo H. M2 bone marrow-derived macrophage-derived exosomes shuffle microRNA-21 to accelerate immune escape of glioma by modulating PEG3. Cancer Cell Int. 2020; 20: 93.

[209] Lu L, Ling W, Ruan Z. TAM-derived extracellular vesicles containing microRNA-29a-3p explain the deterioration of ovarian cancer. Mol Ther Nucleic Acids. 2021; 25: 468-482.

[210] Ye J, Liu X. Macrophage-derived small extracellular vesicles in multiple diseases: biogenesis, function, and therapeutic applications. Front Cell Dev Biol. 2022; 10: 913110.

[211] Zhou W, Zhou Y, Chen X, et al. Pancreatic cancer-targeting exosomes for enhancing immunotherapy and reprogramming tumor microenvironment. Biomaterials. 2021; 268: 120546.

[212] Donoso-Quezada J, Ayala-Mar S, Gonzalez-Valdez J. The role of lipids in exosome biology and intercellular communication: function, analytics and applications. Traffic. 2021; 22(7): 204-220.

[213] Kamerkar S, LeBleu VS, Sugimoto H, et al. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer. Nature. 2017; 546(7659): 498-503.

[214] Qi R, Bai Y, Li K, et al. Cancer-associated fibroblasts suppress ferroptosis and induce gemcitabine resistance in pancreatic cancer cells by secreting exosome-derived ACSL4-targeting miRNAs. Drug Resist Updat. 2023; 68: 100960.

[215] Liu H, Chen L, Liu J, et al. Co-delivery of tumor-derived exosomes with alpha-galactosylceramide on dendritic cell-based immunotherapy for glioblastoma. Cancer Lett. 2017; 411: 182-190.

[216] Manfredi F, di Bonito P, Ridolfi B, et al. The CD8(+) T cell-mediated immunity induced by HPV-E6 uploaded in engineered exosomes is improved by ISCOMATRIX(TM) adjuvant. Vaccines. 2016; 4(4): 42.

[217] Cheng B, Li C, Li J, et al. The activity and immune dynamics of PD-1 inhibition on high-risk pulmonary ground glass opacity lesions: insights from a single-arm, phase II trial. Signal Transduct Target Ther. 2024; 9(1): 93.

[218] Kato T, Mizutani K, Kameyama K, et al. Serum exosomal P-glycoprotein is a potential marker to diagnose docetaxel resistance and select a taxoid for patients with prostate cancer. Urol Oncol. 2015; 33(9): 385. e15-e20.

[219] Lima LG, Leal AC, Vargas G, Porto-Carreiro I, Monteiro RQ. Intercellular transfer of tissue factor via the uptake of tumor-derived microvesicles. Thromb Res. 2013; 132(4): 450-456.

[220] Hao C, Sheng Z, Wang W, et al. Tumor-derived exosomal miR-148b-3p mediates M2 macrophage polarization via TSC2/mTORC1 to promote breast cancer migration and invasion. Thorac Cancer. 2023; 14(16): 1477-1491.

[221] Thery C. Exosomes: secreted vesicles and intercellular communications. F1000 Biol Rep. 2011; 3: 15.

[222] Iero M, Valenti R, Huber V, et al. Tumour-released exosomes and their implications in cancer immunity. Cell Death Differ. 2008; 15(1): 80-88.

[223] Zhang Y, Bi J, Huang J, Tang Y, Du S, Li P. Exosome: a review of its classification, isolation techniques, storage, diagnostic and targeted therapy applications. Int J Nanomed. 2020; 15: 6917-6934.

[224] Zhou M, He X, Mei C, Ou C. Exosome derived from tumor-associated macrophages: biogenesis, functions, and therapeutic implications in human cancers. Biomark Res. 2023; 11(1): 100.

[225] Wei Q, Zhang J, Li Z, Wei L, Ren L. Serum Exo-EphA2 as a potential diagnostic biomarker for pancreatic cancer. Pancreas. 2020; 49(9): 1213-1219.

[226] Li X, Wang Y, Xu C, et al. Analysis of competitive endogenous mechanism and survival prognosis of serum exosomes in ovarian cancer patients based on sequencing technology and bioinformatics. Front Genet. 2022; 13: 850089.

[227] Le Naour J, Zitvogel L, Galluzzi L, Vacchelli E, Kroemer G. Trial watch: sTING agonists in cancer therapy. Oncoimmunology. 2020; 9(1): 1777624.

[228] Aspe JR, Diaz Osterman CJ, Jutzy JM, Deshields S, Whang S, Wall NR. Enhancement of gemcitabine sensitivity in pancreatic adenocarcinoma by novel exosome-mediated delivery of the Survivin-T34A mutant. J Extracell Vesicles. 2014; 3: 23244.

[229] Lee J, Lee H, Goh U, et al. Cellular engineering with membrane fusogenic liposomes to produce functionalized extracellular vesicles. ACS Appl Mater Interfaces. 2016; 8(11): 6790-6795.

[230] Tian Y, Li S, Song J, et al. A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy. Biomaterials. 2014; 35(7): 2383-2390.

[231] Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol. 2011; 29(4): 341-345.

[232] Ohno S, Takanashi M, Sudo K, et al. Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Mol Ther. 2013; 21(1): 185-191.

[233] Nakase I, Futaki S. Combined treatment with a pH-sensitive fusogenic peptide and cationic lipids achieves enhanced cytosolic delivery of exosomes. Sci Rep. 2015; 5: 10112.

[234] Patel G, Agnihotri TG, Gitte M, et al. Exosomes: a potential diagnostic and treatment modality in the quest for counteracting cancer. Cell Oncol. 2023; 46(5): 1159-1179.

[235] Li B, Cao Y, Sun M, Feng H. Expression, regulation, and function of exosome-derived miRNAs in cancer progression and therapy. FASEB J. 2021; 35(10): e21916.

[236] Liu X, Jiang T, Li X, et al. Exosomes transmit T790M mutation-induced resistance in EGFR-mutant NSCLC by activating PI3K/AKT signalling pathway. J Cell Mol Med. 2020; 24(2): 1529-1540.

[237] Si Q, Wu L, Pang D, Jiang P. Exosomes in brain diseases: pathogenesis and therapeutic targets. MedComm. 2023; 4(3): e287.

[238] Feng X, Peng Z, Yuan L, et al. Research progress of exosomes in pathogenesis, diagnosis, and treatment of ocular diseases. Front Bioeng Biotechnol. 2023; 11: 1100310.

[239] Gu WJ, Shen YW, Zhang LJ, et al. The multifaceted involvement of exosomes in tumor progression: induction and inhibition. MedComm. 2021; 2(3): 297-314.

[240] Li K, Chen Y, Li A, Tan C, Liu X. Exosomes play roles in sequential processes of tumor metastasis. Int J Cancer. 2019; 144(7): 1486-1495.

[241] Greening DW, Gopal SK, Mathias RA, et al. Emerging roles of exosomes during epithelial-mesenchymal transition and cancer progression. Semin Cell Dev Biol. 2015; 40: 60-71.

RIGHTS & PERMISSIONS

2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.