REFERENCES
1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71:209-49.
3. Jiang HY, Chen J, Xia CC, Cao LK, Duan T, Song B. Noninvasive imaging of hepatocellular carcinoma: From diagnosis to prognosis. World J Gastroenterol 2018;24:2348-62.
4. Rizzo A, Ricci AD, Brandi G. Systemic adjuvant treatment in hepatocellular carcinoma: tempted to do something rather than nothing. Future Oncol 2020;16:2587-9.
5. Zhang H, Zhang W, Jiang L, Chen Y. Recent advances in systemic therapy for hepatocellular carcinoma. Biomark Res 2022;10:3.
6. Yang C, Zhang H, Zhang L, et al. Evolving therapeutic landscape of advanced hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol 2023;20:203-22.
7. Vafaei S, Zekiy AO, Khanamir RA, et al. Combination therapy with immune checkpoint inhibitors (ICIs); a new frontier. Cancer Cell Int 2022;22:2.
8. Lee MS, Ryoo BY, Hsu CH, et al. Atezolizumab with or without bevacizumab in unresectable hepatocellular carcinoma (GO30140): an open-label, multicentre, phase 1b study. Lancet Oncol 2020;21:808-20.
10. Ladd AD, Duarte S, Sahin I, Zarrinpar A. Mechanisms of drug resistance in HCC. Hepatology 2023:online ahead of print.
11. Gurunathan S, Kang MH, Jeyaraj M, Qasim M, Kim JH. Review of the isolation, characterization, biological function, and multifarious therapeutic approaches of exosomes. Cells 2019;8:307.
12. Wang X, Tian L, Lu JY, Ng IO. Exosomes and cancer-diagnostic and prognostic biomarkers and therapeutic vehicle. Oncogenesis 2022;11:54.
13. Dai J, Su YZ, Zhong SY, et al. Exosomes: key players in cancer and potential therapeutic strategy. Signal Transduct Target Ther 2020;5:145.
14. Zhang PF, Gao C, Huang XY, et al. Cancer cell-derived exosomal circUHRF1 induces natural killer cell exhaustion and may cause resistance to anti-PD1 therapy in hepatocellular carcinoma. Mol Cancer 2020;19:110.
15. Xu J, Ji L, Liang Y, et al. CircRNA-SORE mediates sorafenib resistance in hepatocellular carcinoma by stabilizing YBX1. Signal Transduct Target Ther 2020;5:298.
16. Lu JC, Zhang PF, Huang XY, et al. Amplification of spatially isolated adenosine pathway by tumor-macrophage interaction induces anti-PD1 resistance in hepatocellular carcinoma. J Hematol Oncol 2021;14:200.
17. Zhou Y, Tang W, Zhuo H, et al. Cancer-associated fibroblast exosomes promote chemoresistance to cisplatin in hepatocellular carcinoma through circZFR targeting signal transducers and activators of transcription (STAT3)/nuclear factor -kappa B (NF-κB) pathway. Bioengineered 2022;13:4786-97.
18. Hao X, Zhang Y, Shi X, et al. CircPAK1 promotes the progression of hepatocellular carcinoma via modulation of YAP nucleus localization by interacting with 14-3-3ζ. J Exp Clin Cancer Res 2022;41:281.
19. Hu Z, Chen G, Zhao Y, et al. Exosome-derived circCCAR1 promotes CD8 + T-cell dysfunction and anti-PD1 resistance in hepatocellular carcinoma. Mol Cancer 2023;22:55.
20. He C, Dong X, Zhai B, et al. MiR-21 mediates sorafenib resistance of hepatocellular carcinoma cells by inhibiting autophagy via the PTEN/Akt pathway. Oncotarget 2015;6:28867-81.
21. Lou G, Song X, Yang F, et al. Exosomes derived from miR-122-modified adipose tissue-derived MSCs increase chemosensitivity of hepatocellular carcinoma. J Hematol Oncol 2015;8:122.
22. 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;9:191.
23. Li W, Xin X, Li X, Geng J, Sun Y. Exosomes secreted by M2 macrophages promote cancer stemness of hepatocellular carcinoma via the miR-27a-3p/TXNIP pathways. Int Immunopharmacol 2021;101:107585.
24. Wei XC, Xia YR, Zhou P, et al. Hepatitis B core antigen modulates exosomal miR-135a to target vesicle-associated membrane protein 2 promoting chemoresistance in hepatocellular carcinoma. World J Gastroenterol 2021;27:8302-22.
25. Gao Y, Yin Z, Qi Y, et al. Golgi phosphoprotein 3 promotes angiogenesis and sorafenib resistance in hepatocellular carcinoma via upregulating exosomal miR-494-3p. Cancer Cell Int 2022;22:35.
26. Nakano T, Chen CL, Chen IH, et al. Overexpression of miR-4669 enhances tumor aggressiveness and generates an immunosuppressive tumor microenvironment in hepatocellular carcinoma: its clinical value as a predictive biomarker. Int J Mol Sci 2023;24:7908.
27. Takahashi K, Yan IK, Wood J, Haga H, Patel T. Involvement of extracellular vesicle long noncoding RNA (linc-VLDLR) in tumor cell responses to chemotherapy. Mol Cancer Res 2014;12:1377-87.
28. Takahashi K, Yan IK, Kogure T, Haga H, Patel T. Extracellular vesicle-mediated transfer of long non-coding RNA ROR modulates chemosensitivity in human hepatocellular cancer. FEBS Open Bio 2014;4:458-67.
29. Tey SK, Wong SWK, Chan JYT, et al. Patient pIgR-enriched extracellular vesicles drive cancer stemness, tumorigenesis and metastasis in hepatocellular carcinoma. J Hepatol 2022;76:883-95.
30. Wang X, Huang H, Sze KM, et al. S100A10 promotes HCC development and progression via transfer in extracellular vesicles and regulating their protein cargos. Gut 2023;72:1370-84.
31. Qu Z, Wu J, Wu J, Luo D, Jiang C, Ding Y. Exosomes derived from HCC cells induce sorafenib resistance in hepatocellular carcinoma both in vivo and in vitro. J Exp Clin Cancer Res 2016;35:159.
32. Huang H, Hou J, Liu K, et al. RAB27A-dependent release of exosomes by liver cancer stem cells induces Nanog expression in their differentiated progenies and confers regorafenib resistance. J Gastroenterol Hepatol 2021;36:3429-37.
33. Tang Z, He J, Zou J, Yu S, Sun X, Qin L. Cisplatin-resistant HepG2 cell-derived exosomes transfer cisplatin resistance to cisplatin-sensitive cells in HCC. PeerJ 2021;9:e11200.
34. Negri M, Amatrudo F, Gentile A, et al. Vitamin D Reverts the exosome-mediated transfer of cancer resistance to the mTOR inhibitor everolimus in hepatocellular carcinoma. Front Oncol 2022;12:874091.
35. Huang A, Yang XR, Chung WY, Dennison AR, Zhou J. Targeted therapy for hepatocellular carcinoma. Signal Transduct Target Ther 2020;5:146.
36. Chen J, Jin R, Zhao J, et al. Potential molecular, cellular and microenvironmental mechanism of sorafenib resistance in hepatocellular carcinoma. Cancer Lett 2015;367:1-11.
37. Kudo M, Ikeda M, Takayama T, et al. Safety and efficacy of sorafenib in Japanese patients with hepatocellular carcinoma in clinical practice: a subgroup analysis of GIDEON. J Gastroenterol 2016;51:1150-60.
38. Galle PR. Sorafenib in advanced hepatocellular carcinoma - we have won a battle not the war. J Hepatol 2008;49:871-3.
39. Keating GM, Santoro A. Sorafenib: a review of its use in advanced hepatocellular carcinoma. Drugs 2009;69:223-40.
40. Ping L. Sorafenib plus capecitabine for patients with advanced hepatocellular carcinoma. Available from: https://www.semanticscholar.org/paper/Sorafenib-plus-Capecitabine-for-Patients-with-Ping/7ac9d458ad5c48b9f13dbff60eb7b2f45084854c?utm_source=direct_link [Last accessed on 27 Oct 2023].
41. Bruix J, Qin S, Merle P, et al. RESORCE Investigators. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017;389:56-66.
42. Zhi Y, Abudoureyimu M, Zhou H, et al. FOXM1-mediated LINC-ROR regulates the proliferation and sensitivity to sorafenib in hepatocellular carcinoma. Mol Ther Nucleic Acids 2019;16:576-88.
43. Zhang Y, Zheng J. Functions of immune checkpoint molecules beyond immune evasion. In: Xu J, editor. Regulation of cancer immune checkpoints. Singapore: Springer; 2020. pp. 201-26.
44. Llovet JM, Castet F, Heikenwalder M, et al. Immunotherapies for hepatocellular carcinoma. Nat Rev Clin Oncol 2022;19:151-72.
45. Sangro B, Sarobe P, Hervás-stubbs S, Melero I. Advances in immunotherapy for hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol 2021;18:525-43.
46. Wang Z, Wang Y, Gao P, Ding J. Immune checkpoint inhibitor resistance in hepatocellular carcinoma. Cancer Lett 2023;555:216038.
47. Chen G, Huang AC, Zhang W, et al. Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature 2018;560:382-6.
48. Poggio M, Hu T, Pai CC, et al. Suppression of exosomal PD-L1 induces systemic anti-tumor immunity and memory. Cell 2019;177:414-27.e13.
49. Yang Y, Li CW, Chan LC, et al. Exosomal PD-L1 harbors active defense function to suppress T cell killing of breast cancer cells and promote tumor growth. Cell Res 2018;28:862-4.
50. 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;6:145.
51. Wang X, Shen H, Zhangyuan G, et al. 14-3-3ζ delivered by hepatocellular carcinoma-derived exosomes impaired anti-tumor function of tumor-infiltrating T lymphocytes. Cell Death Dis 2018;9:159.
52. Pu J, Xu Z, Nian J, et al. M2 macrophage-derived extracellular vesicles facilitate CD8+T cell exhaustion in hepatocellular carcinoma via the miR-21-5p/YOD1/YAP/β-catenin pathway. Cell Death Discov 2021;7:182.
53. Xue D, Han J, Liang Z, et al. Current perspectives on the unique roles of exosomes in drug resistance of hepatocellular carcinoma. J Hepatocell Carcinoma 2022;9:99-112.
54. El-Awady R, Saleh E, Hashim A, et al. The Role of eukaryotic and prokaryotic ABC transporter family in failure of chemotherapy. Front Pharmacol 2016;7:535.
55. Chen Z, Shi T, Zhang L, et al. Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: a review of the past decade. Cancer Lett 2016;370:153-64.
56. Bebawy M, Combes V, Lee E, et al. Membrane microparticles mediate transfer of P-glycoprotein to drug sensitive cancer cells. Leukemia 2009;23:1643-9.
57. Levchenko A, Mehta BM, Niu X, et al. Intercellular transfer of P-glycoprotein mediates acquired multidrug resistance in tumor cells. Proc Natl Acad Sci U S A 2005;102:1933-8.
58. Sousa D, Lima RT, Vasconcelos MH. Intercellular transfer of cancer drug resistance traits by extracellular vesicles. Trends Mol Med 2015;21:595-608.
61. Wu Y, Song Y, Wang R, Wang T. Molecular mechanisms of tumor resistance to radiotherapy. Mol Cancer 2023;22:96.
62. Barker HE, Paget JT, Khan AA, Harrington KJ. The tumour microenvironment after radiotherapy: mechanisms of resistance and recurrence. Nat Rev Cancer 2015;15:409-25.
63. Fan Q, Yu Y, Zhou Y, Zhang S, Wu C. An emerging role of radiation‑induced exosomes in hepatocellular carcinoma progression and radioresistance (Review). Int J Oncol 2022;60:46.
64. He D, Zhao Z, Fu B, et al. Exosomes participate in the radiotherapy resistance of cancers. Radiat Res 2022;197:559-65.
65. Ni J, Bucci J, Malouf D, Knox M, Graham P, Li Y. Exosomes in cancer radioresistance. Front Oncol 2019;9:869.
66. Ohri N, Dawson LA, Krishnan S, et al. Radiotherapy for hepatocellular carcinoma: new indications and directions for future study. J Natl Cancer Inst 2016;108:djw133.
67. Arnold CR, Mangesius J, Skvortsova II, Ganswindt U. The role of cancer stem cells in radiation resistance. Front Oncol 2020;10:164.
68. Pu X, Ma S, Gao Y, Xu T, Chang P, Dong L. Mesenchymal stem cell-derived exosomes: biological function and their therapeutic potential in radiation damage. Cells 2020;10:42.
69. Yang Z, Zhong W, Yang L, Wen P, Luo Y, Wu C. The emerging role of exosomes in radiotherapy. Cell Commun Signal 2022;20:171.
70. Fang X, Yan Q, Liu S, Guan XY. Cancer stem cells in hepatocellular carcinoma: intrinsic and extrinsic molecular mechanisms in stemness regulation. Int J Mol Sci 2022;23:12327.
71. Lee TK, Guan XY, Ma S. Cancer stem cells in hepatocellular carcinoma - from origin to clinical implications. Nat Rev Gastroenterol Hepatol 2022;19:26-44.
72. Ma S, Lee TK, Zheng BJ, Chan KW, Guan XY. CD133+ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway. Oncogene 2008;27:1749-58.
73. Dongre A, Weinberg RA. New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer. Nat Rev Mol Cell Biol 2019;20:69-84.
74. Syn N, Wang L, Sethi G, Thiery JP, Goh BC. Exosome-mediated metastasis: from epithelial-mesenchymal transition to escape from immunosurveillance. Trends Pharmacol Sci 2016;37:606-17.
75. Chen L, Guo P, He Y, et al. HCC-derived exosomes elicit HCC progression and recurrence by epithelial-mesenchymal transition through MAPK/ERK signalling pathway. Cell Death Dis 2018;9:513.
76. Karaosmanoğlu O, Banerjee S, Sivas H. Identification of biomarkers associated with partial epithelial to mesenchymal transition in the secretome of slug over-expressing hepatocellular carcinoma cells. Cell Oncol 2018;41:439-53.
77. Shi CJ, Lv MY, Deng LQ, Zeng WQ, Fu WM, Zhang JF. Linc-ROR drive adriamycin resistance by targeting AP-2α/Wnt/β-catenin axis in hepatocellular carcinoma. Cell Biol Toxicol 2023;39:1735-52.
78. Lin Q, Zhou CR, Bai MJ, et al. Exosome-mediated miRNA delivery promotes liver cancer EMT and metastasis. Am J Transl Res 2020;12:1080-95.
79. Sun H, Wang C, Hu B, et al. Exosomal S100A4 derived from highly metastatic hepatocellular carcinoma cells promotes metastasis by activating STAT3. Signal Transduct Target Ther 2021;6:187.
80. He R, Wang Z, Shi W, et al. Exosomes in hepatocellular carcinoma microenvironment and their potential clinical application value. Biomed Pharmacother 2021;138:111529.
81. Wu Y, Zhang J, Li Q. Autophagy, an accomplice or antagonist of drug resistance in HCC? Cell Death Dis 2021;12:266.
82. Liu L, Liao JZ, He XX, Li PY. The role of autophagy in hepatocellular carcinoma: friend or foe. Oncotarget 2017;8:57707-22.
83. Huang F, Wang BR, Wang YG. Role of autophagy in tumorigenesis, metastasis, targeted therapy and drug resistance of hepatocellular carcinoma. World J Gastroenterol 2018;24:4643-51.
84. Shi YH, Ding ZB, Zhou J, et al. Targeting autophagy enhances sorafenib lethality for hepatocellular carcinoma via ER stress-related apoptosis. Autophagy 2011;7:1159-72.
85. Zhang K, Chen J, Zhou H, et al. PU.1/microRNA-142-3p targets ATG5/ATG16L1 to inactivate autophagy and sensitize hepatocellular carcinoma cells to sorafenib. Cell Death Dis 2018;9:312.
86. Guo XL, Li D, Sun K, et al. Inhibition of autophagy enhances anticancer effects of bevacizumab in hepatocarcinoma. J Mol Med 2013;91:473-83.
87. Liu DX, Li PP, Guo JP, et al. Exosomes derived from HBV-associated liver cancer promote chemoresistance by upregulating chaperone-mediated autophagy. Oncol Lett 2019;17:323-31.
88. Tian XP, Wang CY, Jin XH, et al. Acidic microenvironment up-regulates exosomal mir-21 and mir-10b in early-stage hepatocellular carcinoma to promote cancer cell proliferation and metastasis. Theranostics 2019;9:1965-79.
89. Yao M, Liang S, Cheng B. Role of exosomes in hepatocellular carcinoma and the regulation of traditional Chinese medicine. Front Pharmacol 2023;14:1110922.
90. Huang M, Huang X, Huang N. Exosomal circGSE1 promotes immune escape of hepatocellular carcinoma by inducing the expansion of regulatory T cells. Cancer Sci 2022;113:1968-83.
91. Li C, Xu X. Biological functions and clinical applications of exosomal non-coding RNAs in hepatocellular carcinoma. Cell Mol Life Sci 2019;76:4203-19.
92. Yao Z, Jia C, Tai Y, et al. Serum exosomal long noncoding RNAs lnc-FAM72D-3 and lnc-EPC1-4 as diagnostic biomarkers for hepatocellular carcinoma. Aging 2020;12:11843-63.
93. Ji W, Bai J, Ke Y. Exosomal ZFPM2-AS1 contributes to tumorigenesis, metastasis, stemness, macrophage polarization, and infiltration in hepatocellular carcinoma through PKM mediated glycolysis. Environ Toxicol 2023;38:1332-46.
94. Hoshino A, Kim HS, Bojmar L, et al. Extracellular vesicle and particle biomarkers define multiple human cancers. Cell 2020;182:1044-61.e18.
95. Li R, Dong C, Jiang K, et al. Rab27B enhances drug resistance in hepatocellular carcinoma by promoting exosome-mediated drug efflux. Carcinogenesis 2020;41:1583-91.
96. Zhang H, Lu J, Liu J, Zhang G, Lu A. Advances in the discovery of exosome inhibitors in cancer. J Enzyme Inhib Med Chem 2020;35:1322-30.
97. Kim JH, Lee CH, Baek MC. Dissecting exosome inhibitors: therapeutic insights into small-molecule chemicals against cancer. Exp Mol Med 2022;54:1833-43.
98. Xu R, Rai A, Chen M, Suwakulsiri W, Greening DW, Simpson RJ. Extracellular vesicles in cancer - implications for future improvements in cancer care. Nat Rev Clin Oncol 2018;15:617-38.
99. Meng W, He C, Hao Y, Wang L, Li L, Zhu G. Prospects and challenges of extracellular vesicle-based drug delivery system: considering cell source. Drug Deliv 2020;27:585-98.
100. Herrmann IK, Wood MJA, Fuhrmann G. Extracellular vesicles as a next-generation drug delivery platform. Nat Nanotechnol 2021;16:748-59.
102. Lou G, Chen L, Xia C, et al. MiR-199a-modified exosomes from adipose tissue-derived mesenchymal stem cells improve hepatocellular carcinoma chemosensitivity through mTOR pathway. J Exp Clin Cancer Res 2020;39:4.
103. Li H, Yang C, Shi Y, Zhao L. Exosomes derived from siRNA against GRP78 modified bone-marrow-derived mesenchymal stem cells suppress Sorafenib resistance in hepatocellular carcinoma. J Nanobiotechnol 2018;16:103.
104. Deng J, Ke H. Overcoming the resistance of hepatocellular carcinoma to PD-1/PD-L1 inhibitor and the resultant immunosuppression by CD38 siRNA-loaded extracellular vesicles. Oncoimmunology 2023;12:2152635.
105. He C, Jaffar Ali D, Qi Y, et al. Engineered extracellular vesicles mediated CRISPR-induced deficiency of IQGAP1/FOXM1 reverses sorafenib resistance in HCC by suppressing cancer stem cells. J Nanobiotechnol 2023;21:154.
106. Kim MS, Haney MJ, Zhao Y, et al. Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells. Nanomedicine 2016;12:655-64.
