REFERENCES
2. Anwanwan D, Singh SK, Singh S, Saikam V, Singh R. Challenges in liver cancer and possible treatment approaches. Biochim Biophys Acta Rev Cancer 2020;1873:188314.
4. Nishida N, Kudo M. Oncogenic signal and tumor microenvironment in hepatocellular carcinoma. Oncology 2017;93 Suppl 1:160-4.
5. Donne R, Lujambio A. The liver cancer immune microenvironment: therapeutic implications for hepatocellular carcinoma. Hepatology 2023;77:1773-96.
6. Li H, Li J, Qu X, et al. Establishment and validation of a novel lysosome-related gene signature for predicting prognosis and immune landscape in hepatocellular carcinoma. J Cancer Res Clin Oncol 2023;149:17543-57.
7. Li X, Ramadori P, Pfister D, Seehawer M, Zender L, Heikenwalder M. The immunological and metabolic landscape in primary and metastatic liver cancer. Nat Rev Cancer 2021;21:541-57.
8. Degasperi E, Colombo M. Distinctive features of hepatocellular carcinoma in non-alcoholic fatty liver disease. Lancet Gastroenterol Hepatol 2016;1:156-64.
9. Marengo A, Rosso C, Bugianesi E. Liver cancer: connections with obesity, fatty liver, and cirrhosis. Annu Rev Med 2016;67:103-17.
10. Sim HW, Knox J. Hepatocellular carcinoma in the era of immunotherapy. Curr Probl Cancer 2018;42:40-8.
11. Pennock GK, Chow LQ. The evolving role of immune checkpoint inhibitors in cancer treatment. Oncologist 2015;20:812-22.
12. Reig M, Forner A, Rimola J, et al. BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update. J Hepatol 2022;76:681-93.
13. Galluzzi L, Humeau J, Buqué A, Zitvogel L, Kroemer G. Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors. Nat Rev Clin Oncol 2020;17:725-41.
14. Xing R, Gao J, Cui Q, Wang Q. Strategies to improve the antitumor effect of immunotherapy for hepatocellular carcinoma. Front Immunol 2021;12:783236.
15. Shi C, Qin K, Lin A, et al. The role of DNA damage repair (DDR) system in response to immune checkpoint inhibitor (ICI) therapy. J Exp Clin Cancer Res 2022;41:268.
16. Rizzo A, Ricci AD. PD-L1, TMB, and other potential predictors of response to immunotherapy for hepatocellular carcinoma: how can they assist drug clinical trials? Expert Opin Investig Drugs 2022;31:415-23.
19. Cleary JM, Aguirre AJ, Shapiro GI, D’Andrea AD. Biomarker-guided development of DNA repair inhibitors. Mol Cell 2020;78:1070-85.
20. Jiang M, Jia K, Wang L, et al. Alterations of DNA damage response pathway: biomarker and therapeutic strategy for cancer immunotherapy. Acta Pharm Sin B 2021;11:2983-94.
21. DuBray BJ, Jr. , Chapman WC, Anderson CD. Hepatocellular carcinoma: a review of the surgical approaches to management. Mo Med 2011;108:195-8.
22. Worlikar T, Mendiratta-Lala M, Vlaisavljevich E, et al. Effects of histotripsy on local tumor progression in an in vivo orthotopic rodent liver tumor model. BME Front 2020;2020:9830304.
23. O'Leary C, Mahler M, Soulen MC. Curative-intent therapies in localized hepatocellular carcinoma. Curr Treat Options Oncol 2020;21:31.
24. Hartke J, Johnson M, Ghabril M. The diagnosis and treatment of hepatocellular carcinoma. Semin Diagn Pathol 2017;34:153-9.
25. Sunaga N, Miura Y, Kasahara N, Sakurai R. Targeting oncogenic KRAS in non-small-cell lung cancer. Cancers 2021;13:5956.
26. Greten TF, Lai CW, Li G, Staveley-O’Carroll KF. Targeted and Immune-Based Therapies for Hepatocellular Carcinoma. Gastroenterology 2019;156:510-24.
27. Chang Y, Jeong SW, Young Jang J, Jae Kim Y. Recent updates of transarterial chemoembolilzation in hepatocellular carcinoma. Int J Mol Sci 2020;21:8165.
28. Chiang CL, Chiu KWH, Chan KSK, et al. Sequential transarterial chemoembolisation and stereotactic body radiotherapy followed by immunotherapy as conversion therapy for patients with locally advanced, unresectable hepatocellular carcinoma (START-FIT): a single-arm, phase 2 trial. Lancet Gastroenterol Hepatol 2023;8:169-78.
29. Li SH, Mei J, Cheng Y, et al. Postoperative adjuvant hepatic arterial infusion chemotherapy with FOLFOX in hepatocellular carcinoma with microvascular invasion: a multicenter, phase III, randomized study. J Clin Oncol 2023;41:1898-908.
30. Yuan Y, He W, Yang Z, et al. TACE-HAIC combined with targeted therapy and immunotherapy versus TACE alone for hepatocellular carcinoma with portal vein tumour thrombus: a propensity score matching study. Int J Surg 2023;109:1222-30.
31. Zhu ZX, Huang JW, Liao MH, Zeng Y. Treatment strategy for hepatocellular carcinoma in China: radiofrequency ablation versus liver resection. Jpn J Clin Oncol 2016;46:1075-80.
32. Wang J, Wu D, Sun M, et al. Deep segmentation feature-based radiomics improves recurrence prediction of hepatocellular carcinoma. BME Front 2022;2022:9793716.
33. Feng M, Ben-Josef E. Radiation therapy for hepatocellular carcinoma. Semin Radiat Oncol 2011;21:271-7.
34. Sanuki N, Takeda A, Oku Y, et al. Stereotactic body radiotherapy for small hepatocellular carcinoma: a retrospective outcome analysis in 185 patients. Acta Oncol 2014;53:399-404.
35. Wu F, Chen B, Dong D, et al. Phase 2 evaluation of neoadjuvant intensity-modulated radiotherapy in centrally located hepatocellular carcinoma: a nonrandomized controlled trial. JAMA Surg 2022;157:1089-96.
36. Huang A, Yang XR, Chung WY, Dennison AR, Zhou J. Targeted therapy for hepatocellular carcinoma. Signal Transduct Target Ther 2020;5:146.
37. Feng MY, Chan LL, Chan SL. Drug treatment for advanced hepatocellular carcinoma: first-line and beyond. Curr Oncol 2022;29:5489-507.
38. Obi S, Yoshida H, Toune R, et al. Combination therapy of intraarterial 5-fluorouracil and systemic interferon-alpha for advanced hepatocellular carcinoma with portal venous invasion. Cancer 2006;106:1990-7.
39. Oura K, Morishita A, Tani J, Masaki T. Tumor immune microenvironment and immunosuppressive therapy in hepatocellular carcinoma: a review. Int J Mol Sci 2021;22:5801.
40. Sharma A, Seow JJW, Dutertre CA, et al. Onco-fetal reprogramming of endothelial cells drives immunosuppressive macrophages in hepatocellular carcinoma. Cell 2020;183:377-94.e21.
41. Lee HW, Cho KJ, Park JY. Current status and future direction of immunotherapy in hepatocellular carcinoma: what do the data suggest? Immune Netw 2020;20:e11.
42. Chen C, Wang Z, Ding Y, Qin Y. Tumor microenvironment-mediated immune evasion in hepatocellular carcinoma. Front Immunol 2023;14:1133308.
43. Sangro B, Sarobe P, Hervás-Stubbs S, Melero I. Advances in immunotherapy for hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol 2021;18:525-43.
44. De Martin E, Michot JM, Papouin B, et al. Characterization of liver injury induced by cancer immunotherapy using immune checkpoint inhibitors. J Hepatol 2018;68:1181-90.
45. Chamoto K, Al-habsi M, Honjo T. Role of PD-1 in immunity and diseases. In: Yoshimura A, editor. Emerging concepts targeting immune checkpoints in cancer and autoimmunity. Cham: Springer International Publishing; 2017. pp. 75-97.
46. Sato H, Jeggo PA, Shibata A. Regulation of programmed death-ligand 1 expression in response to DNA damage in cancer cells: Implications for precision medicine. Cancer Sci 2019;110:3415-23.
47. Li Q, Han J, Yang Y, Chen Y. PD-1/PD-L1 checkpoint inhibitors in advanced hepatocellular carcinoma immunotherapy. Front Immunol 2022;13:1070961.
49. Liu Y, Cheng Y, Xu Y, et al. Increased expression of programmed cell death protein 1 on NK cells inhibits NK-cell-mediated anti-tumor function and indicates poor prognosis in digestive cancers. Oncogene 2017;36:6143-53.
50. Shiravand Y, Khodadadi F, Kashani SMA, et al. Immune checkpoint inhibitors in cancer therapy. Curr Oncol 2022;29:3044-60.
51. Kudo M, Finn RS, Edeline J, et al. KEYNOTE-224 Investigators. Updated efficacy and safety of KEYNOTE-224: a phase II study of pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib. Eur J Cancer 2022;167:1-12.
52. Castria TB, Khalil DN, Harding JJ, O'Reilly EM, Abou-Alfa GK. Tremelimumab and durvalumab in the treatment of unresectable, advanced hepatocellular carcinoma. Future Oncol 2022;18:3769-82.
53. Xiang YJ, Wang K, Yu HM, et al. Transarterial chemoembolization plus a PD-1 inhibitor with or without lenvatinib for intermediate-stage hepatocellular carcinoma. Hepatol Res 2022;52:721-9.
54. Finn RS, Zhu AX. Evolution of Systemic Therapy for Hepatocellular Carcinoma. Hepatology 2021;73 Suppl 1:150-7.
55. Mody K, Abou-Alfa GK. Systemic Therapy for Advanced Hepatocellular Carcinoma in an Evolving Landscape. Curr Treat Options Oncol 2019;20:3.
56. Qin S, Chan SL, Gu S, et al. CARES-310 Study Group. Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310): a randomised, open-label, international phase 3 study. Lancet 2023;402:1133-46.
57. Kaufmann DE, Kavanagh DG, Pereyra F, et al. Upregulation of CTLA-4 by HIV-specific CD4+ T cells correlates with disease progression and defines a reversible immune dysfunction. Nat Immunol 2007;8:1246-54.
58. Song X, Kelley RK, Khan AA, et al. Exposure-response analyses of tremelimumab monotherapy or in combination with durvalumab in patients with unresectable hepatocellular carcinoma. Clin Cancer Res 2023;29:754-63.
59. Zhao M, Duan X, Mi L, et al. Prognosis of hepatocellular carcinoma and its association with immune cells using systemic inflammatory response index. Future Oncol 2022;18:2269-88.
60. Yau T, Kang YK, Kim TY, et al. Efficacy and safety of nivolumab plus ipilimumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib: the checkmate 040 randomized clinical trial. JAMA Oncol 2020;6:e204564.
61. Li X, Fu Z, Chen X, et al. Efficacy and safety of lenvatinib combined with PD-1 inhibitors plus TACE for unresectable hepatocellular carcinoma patients in china real-world. Front Oncol 2022;12:950266.
62. Li L, Liu HT, Teng YX, et al. Second-line treatment options for hepatocellular carcinoma: current state and challenges for the future. Expert Opin Investig Drugs 2022;31:1151-67.
63. Finn RS, Qin S, Ikeda M, et al. IMbrave150 Investigators. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med 2020;382:1894-905.
64. Liu X, Lu Y, Qin S. Atezolizumab and bevacizumab for hepatocellular carcinoma: mechanism, pharmacokinetics and future treatment strategies. Future Oncol 2021;17:2243-56.
65. Xin Y, Zhang X, Liu N, et al. Efficacy and safety of lenvatinib plus PD-1 inhibitor with or without transarterial chemoembolization in unresectable hepatocellular carcinoma. Hepatol Int 2023;17:753-64.
66. Mei J, Tang YH, Wei W, et al. Hepatic arterial infusion chemotherapy combined with PD-1 inhibitors plus lenvatinib versus pd-1 inhibitors plus lenvatinib for advanced hepatocellular carcinoma. Front Oncol 2021;11:618206.
67. He MK, Liang RB, Zhao Y, et al. Lenvatinib, toripalimab, plus hepatic arterial infusion chemotherapy versus lenvatinib alone for advanced hepatocellular carcinoma. Ther Adv Med Oncol 2021;13:17588359211002720.
68. Hong Y, Feng Y, Sun H, et al. Tislelizumab uniquely binds to the CC' loop of PD-1 with slow-dissociated rate and complete PD-L1 blockage. FEBS Open Bio 2021;11:782-92.
69. Xiao Y, Zhu G, Xie J, et al. Pretreatment neutrophil-to-lymphocyte ratio as prognostic biomarkers in patients with unresectable hepatocellular carcinoma treated with hepatic arterial infusion chemotherapy combined with lenvatinib and camrelizumab. J Hepatocell Carcinoma 2023;10:2049-58.
70. Qin S, Finn RS, Kudo M, et al. RATIONALE 301 study: tislelizumab versus sorafenib as first-line treatment for unresectable hepatocellular carcinoma. Future Oncol 2019;15:1811-22.
71. Qin S, Ren Z, Meng Z, et al. Camrelizumab in patients with previously treated advanced hepatocellular carcinoma: a multicentre, open-label, parallel-group, randomised, phase 2 trial. Lancet Oncol 2020;21:571-80.
72. Yau T, Park JW, Finn RS, et al. Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol 2022;23:77-90.
73. Merle P, Kudo M, Edeline J, et al. Pembrolizumab as second-line therapy for advanced hepatocellular carcinoma: longer term follow-up from the phase 3 KEYNOTE-240 trial. Liver Cancer 2023;12:309-20.
74. Zhao Y, Zhang YN, Wang KT, Chen L. Lenvatinib for hepatocellular carcinoma: from preclinical mechanisms to anti-cancer therapy. Biochim Biophys Acta Rev Cancer 2020;1874:188391.
75. Chen R, Ielasi L, di Carlo A, Tovoli F. Donafenib in hepatocellular carcinoma. Drugs Today 2023;59:83-90.
76. Llovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma. Nat Rev Dis Primers 2021;7:6.
77. Kim HD, Jung S, Lim HY, et al. Regorafenib plus nivolumab in unresectable hepatocellular carcinoma: the phase 2 RENOBATE trial. Nat Med 2024;30:699-707.
78. Ren Z, Xu J, Bai Y, et al. ORIENT-32 study group. Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2-3 study. Lancet Oncol 2021;22:977-90.
79. Zhang T, Merle P, Wang H, Zhao H, Kudo M. Combination therapy for advanced hepatocellular carcinoma: do we see the light at the end of the tunnel? Hepatobiliary Surg Nutr 2021;10:180-92.
80. Yau T, Zagonel V, Santoro A, et al. Nivolumab plus cabozantinib with or without ipilimumab for advanced hepatocellular carcinoma: results from cohort 6 of the CheckMate 040 trial. J Clin Oncol 2023;41:1747-57.
81. Hatanaka T, Yata Y, Naganuma A, Kakizaki S. Treatment strategy for intermediate-stage hepatocellular carcinoma: transarterial chemoembolization, systemic therapy, and conversion therapy. Cancers 2023;15:1798.
82. Chatterjee N, Walker GC. Mechanisms of DNA damage, repair, and mutagenesis. Environ Mol Mutagen 2017;58:235-63.
83. Vickridge E, Faraco CCF, Nepveu A. Base excision repair accessory factors in senescence avoidance and resistance to treatments. Cancer Drug Resist 2022;5:703-20.
84. Li Z, Pearlman AH, Hsieh P. DNA mismatch repair and the DNA damage response. DNA Repair 2016;38:94-101.
85. Li W, Jones K, Burke TJ, Hossain MA, Lariscy L. Epigenetic regulation of nucleotide excision repair. Front Cell Dev Biol 2022;10:847051.
86. Wright WD, Shah SS, Heyer WD. Homologous recombination and the repair of DNA double-strand breaks. J Biol Chem 2018;293:10524-35.
87. Chang HHY, Pannunzio NR, Adachi N, Lieber MR. Non-homologous DNA end joining and alternative pathways to double-strand break repair. Nat Rev Mol Cell Biol 2017;18:495-506.
88. Wang Z, Zhao J, Wang G, et al. Comutations in DNA damage response pathways serve as potential biomarkers for immune checkpoint blockade. Cancer Res 2018;78:6486-96.
89. Bai Y, He J, Ma Y, Liang H, Li M, Wu Y. Identification of DNA repair gene signature and potential molecular subtypes in hepatocellular carcinoma. Front Oncol 2023;13:1180722.
90. Chen Y, Wang X, Deng X, et al. DNA damage repair status predicts opposite clinical prognosis immunotherapy and non-immunotherapy in hepatocellular carcinoma. Front Immunol 2021;12:676922.
91. Lin P, Gao RZ, Wen R, He Y, Yang H. DNA damage repair profiles alteration characterize a hepatocellular carcinoma subtype with unique molecular and clinicopathologic features. Front Immunol 2021;12:715460.
92. Li H, Liu ZY, Wu N, Chen YC, Cheng Q, Wang J. PARP inhibitor resistance: the underlying mechanisms and clinical implications. Mol Cancer 2020;19:107.
93. Singh MP, Cho HJ, Kim JT, Baek KE, Lee HG, Kang SC. Morin hydrate reverses cisplatin resistance by impairing PARP1/HMGB1-dependent autophagy in hepatocellular carcinoma. Cancers 2019;11:986.
94. Tong Y, Wang F, Li S, et al. Histone methyltransferase KMT5C drives liver cancer progression and directs therapeutic response to PARP inhibitors. Hepatology 2023; doi: 10.1097/hep.0000000000000559.
95. Wang M, Chen S, Ao D. Targeting DNA repair pathway in cancer: mechanisms and clinical application. MedComm 2021;2:654-91.
96. Baxter JS, Zatreanu D, Pettitt SJ, Lord CJ. Resistance to DNA repair inhibitors in cancer. Mol Oncol 2022;16:3811-27.
97. Groelly FJ, Fawkes M, Dagg RA, Blackford AN, Tarsounas M. Targeting DNA damage response pathways in cancer. Nat Rev Cancer 2023;23:78-94.
98. Cheng B, Pan W, Xing Y, Xiao Y, Chen J, Xu Z. Recent advances in DDR (DNA damage response) inhibitors for cancer therapy. Eur J Med Chem 2022;230:114109.
99. Reisländer T, Groelly FJ, Tarsounas M. DNA damage and cancer immunotherapy: a STING in the tale. Mol Cell 2020;80:21-8.
100. Yang XD, Kong FE, Qi L, et al. PARP inhibitor Olaparib overcomes Sorafenib resistance through reshaping the pluripotent transcriptome in hepatocellular carcinoma. Mol Cancer 2021;20:20.
101. Hunia J, Gawalski K, Szredzka A, Suskiewicz MJ, Nowis D. The potential of PARP inhibitors in targeted cancer therapy and immunotherapy. Front Mol Biosci 2022;9:1073797.
102. Vikas P, Borcherding N, Chennamadhavuni A, Garje R. Therapeutic potential of combining PARP inhibitor and immunotherapy in solid tumors. Front Oncol 2020;10:570.
103. Sun G, Miao G, Li Z, et al. Inhibition of PARP potentiates immune checkpoint therapy through miR-513/PD-L1 pathway in hepatocellular carcinoma. J Oncol 2022;2022:6988923.
105. Sheng H, Huang Y, Xiao Y, et al. ATR inhibitor AZD6738 enhances the antitumor activity of radiotherapy and immune checkpoint inhibitors by potentiating the tumor immune microenvironment in hepatocellular carcinoma. J Immunother Cancer 2020;8:e000340.
106. Guo Y, Wang J, Benedict B, et al. Targeting CDC7 potentiates ATR-CHK1 signaling inhibition through induction of DNA replication stress in liver cancer. Genome Med 2021;13:166.
107. Benson AB, D’Angelica MI, Abbott DE, et al. Hepatobiliary cancers, version 2.2021, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 2021;19:541-65.
108. Xu J, Shen J, Gu S, et al. Camrelizumab in combination with apatinib in patients with advanced hepatocellular carcinoma (RESCUE): a nonrandomized, open-label, phase II trial. Clin Cancer Res 2021;27:1003-11.
109. Sen T, Rodriguez BL, Chen L, et al. Targeting DNA damage response promotes antitumor immunity through STING-mediated T-cell activation in small cell lung cancer. Cancer Discov 2019;9:646-61.
110. Qiu Z, Oleinick NL, Zhang J. ATR/CHK1 inhibitors and cancer therapy. Radiother Oncol 2018;126:450-64.
111. Drew Y, Kim JW, Penson RT, et al. MEDIOLA Investigators. Olaparib plus durvalumab, with or without bevacizumab, as treatment in PARP inhibitor-naïve platinum-sensitive relapsed ovarian cancer: a phase ii multi-cohort study. Clin Cancer Res 2024;30:50-62.
112. Konstantinopoulos PA, Waggoner S, Vidal GA, et al. Single-arm phases 1 and 2 trial of niraparib in combination with pembrolizumab in patients with recurrent platinum-resistant ovarian carcinoma. JAMA Oncol 2019;5:1141-9.
113. Konyn P, Ahmed A, Kim D. Current epidemiology in hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol 2021;15:1295-307.
114. Yang WS, Zeng XF, Liu ZN, et al. Diet and liver cancer risk: a narrative review of epidemiological evidence. Br J Nutr 2020;124:330-40.
115. Ogino S, Lochhead P, Chan AT, et al. Molecular pathological epidemiology of epigenetics: emerging integrative science to analyze environment, host, and disease. Mod Pathol 2013;26:465-84.
116. Li L, Wang H. Heterogeneity of liver cancer and personalized therapy. Cancer Lett 2016;379:191-7.
117. Chuang SC, La Vecchia C, Boffetta P. Liver cancer: descriptive epidemiology and risk factors other than HBV and HCV infection. Cancer Lett 2009;286:9-14.
118. Ueyama M, Nishida N, Korenaga M, et al. The impact of PNPLA3 and JAZF1 on hepatocellular carcinoma in non-viral hepatitis patients with type 2 diabetes mellitus. J Gastroenterol 2016;51:370-9.
119. Cichoż-Lach H, Michalak A. Oxidative stress as a crucial factor in liver diseases. World J Gastroenterol 2014;20:8082-91.
120. Cesaratto L, Vascotto C, Calligaris S, Tell G. The importance of redox state in liver damage. Ann Hepatol 2004;3:86-92.
121. Wang X, Tian Y, Lin H, Cao X, Zhang Z. Curcumin induces apoptosis in human hepatocellular carcinoma cells by decreasing the expression of STAT3/VEGF/HIF-1α signaling. Open Life Sci 2023;18:20220618.
122. Karabekir SC, Özgörgülü A. Possible protective effects of resveratrol in hepatocellular carcinoma. Iran J Basic Med Sci 2020;23:71-8.
