AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
Powered by AMiner. Clicking this button will take you away from SciOpen.
Home iLIVER Article
Article Link
Cite
EndNote(RIS) BibTeX
Collect
Submit Manuscript
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Review | Open Access

Emerging role of molecular diagnosis and personalized therapy for hepatocellular carcinoma

Ming-Da Wanga,1, Yong-Kang Diaoa,1, Lan-Qing Yaoa,1, Zhong-Qi Fanb,1, Ke-Chun Wanga, Han Wua, Li-Hui Gua, Jia-Hao Xua, Chao Lia, Guo-Yue Lvb( ), Tian Yanga,b( )
Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai 200438, China
Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, First Hospital of Jilin University, Changchun 130021, China

1 These authors contributed equally to this work.

Show Author Information

Abstract

Hepatocellular carcinoma (HCC) is a prevalent malignancy worldwide, ranking as the sixth most common malignancy and the third leading cause of cancer-related mortality. Late diagnosis, limited management options, and its complex etiology contribute to the poor prognosis and high mortality rates. Recent advances in understanding the molecular mechanisms of HCC and innovations in high-throughput sequencing technologies have led to the development of molecular diagnostics and personalized therapies for this challenging malignancy. This review provides a comprehensive overview of research on the molecular diagnosis and individualized treatment for HCC. We highlight key advances and potential future directions and discuss the application of next-generation sequencing technologies to identify and characterize genetic and epigenetic alterations in HCC patients. These technologies may aid in the selection of targeted therapies, prediction of treatment response, and monitoring disease progression. Furthermore, we explore the role of liquid biopsy in HCC diagnosis, prognosis prediction, and treatment monitoring, focusing on circulating tumor cells, circulating tumor DNA, and extracellular vesicles. We also explore the evolving landscape of personalized therapy for HCC, including targeted therapies against key oncogenic signaling pathways, immune checkpoint inhibitors, tumor-agnostic therapies, and innovative cellbased therapies. We discuss the challenges and opportunities that lie ahead in the quest to improve HCC patient outcomes through the integration of molecular diagnostics and individualized precision therapies. We emphasize the need for multi-interdisciplinary collaboration, refinement of predictive and prognostic biomarkers, and the development of more effective combination strategies for HCC management in the new area of precision medicine.

Keywords

DiagnosisTargeted therapyHepatocellular carcinomaImmune checkpoint inhibitorsLiquid biopsy

References

[1]

Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA A Cancer J Clin 2018;68(6):394–424. https://doi.org/10.3322/caac.21492.
Crossref Google Scholar
[2]

Vogel A, Meyer T, Sapisochin G, et al. Hepatocellular carcinoma. Lancet 2022; 400(10360):1345–62. https://doi.org/10.1016/S0140-6736(22)01200-4.
Crossref Google Scholar
[3]

Mak LY, Cruz-Ramón V, Chinchilla-López P, et al. Global epidemiology, prevention, and management of hepatocellular carcinoma. Am Soc Clin Oncol Educ Book 2018;38:262–79. https://doi.org/10.1200/EDBK_200939.
Crossref Google Scholar
[4]

Rumgay H, Arnold M, Ferlay J, et al. Global burden of primary liver cancer in 2020 and predictions to 2040. J Hepatol 2022;77(6):1598–606. https://doi.org/10.1016/j.jhep.2022.08.021.
Crossref Google Scholar
[5]

Reig M, Forner A, Rimola J, et al. BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update. J Hepatol 2022;76(3):681–93. https://doi.org/10.1016/j.jhep.2021.11.018.
Crossref Google Scholar
[6]

Yang JD, Roberts LR. Hepatocellular carcinoma: a global view. Nat Rev Gastroenterol Hepatol 2010;7(8):448–58. https://doi.org/10.1038/nrgastro.2010.100.
Crossref Google Scholar
[7]

Zucman-Rossi J, Villanueva A, Nault JC, et al. Genetic landscape and biomarkers of hepatocellular carcinoma. Gastroenterology 2015;149(5):1226. https://doi.org/10.1053/j.gastro.2015.05.061.39.e4.
Crossref Google Scholar
[8]

Schulze K, Imbeaud S, Letouzé E, et al. Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets. Nat Genet 2015;47(5):505–11. https://doi.org/10.1038/ng.3252.
Crossref Google Scholar
[9]

Lu X, Paliogiannis P, Calvisi DF, et al. Role of the mammalian target of rapamycin pathway in liver cancer: from molecular genetics to targeted therapies. Hepatology 2021;73(Suppl 1):49–61. https://doi.org/10.1002/hep.31310.
Crossref Google Scholar
[10]

Bang J, Jun M, Lee S, et al. Targeting EGFR/PI3K/AKT/mTOR signaling in hepatocellular carcinoma. Pharmaceutics 2023;15(8):2130. https://doi.org/10.3390/pharmaceutics15082130.
Crossref Google Scholar
[11]

Shen Y, Zheng X, Qian Y, et al. Interactions between driver genes shape the signaling pathway landscape and direct hepatocellular carcinoma therapy. Cancer Sci 2023;114(6):2386–99. https://doi.org/10.1111/cas.15788.
Crossref Google Scholar
[12]

Llovet JM, Montal R, Sia D, et al. Molecular therapies and precision medicine for hepatocellular carcinoma. Nat Rev Clin Oncol 2018;15(10):599–616. https://doi.org/10.1038/s41571-018-0073-4.
Crossref Google Scholar
[13]

Yang JD, Hainaut P, Gores GJ, et al. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol 2019; 16(10):589–604. https://doi.org/10.1038/s41575-019-0186-y.
Crossref Google Scholar
[14]

Marrero JA, Kulik LM, Sirlin CB, et al. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American association for the study of liver diseases. Hepatology 2018;68(2):723–50. https://doi.org/10.1002/hep.29913.
Crossref Google Scholar
[15]

Yang T, Wang MD, Xu XF, et al. Management of hepatocellular carcinoma in China: seeking common grounds while reserving differences. Clin Mol Hepatol 2023;29(2):342–4. https://doi.org/10.3350/cmh.2023.0106.
Crossref Google Scholar
[16]

Tzartzeva K, Obi J, Rich NE, et al. Surveillance imaging and alpha fetoprotein for early detection of hepatocellular carcinoma in patients with cirrhosis: a metaanalysis. Gastroenterology 2018;154(6):1706–17018.e1. https://doi.org/10.1053/j.gastro.2018.01.064.
Crossref Google Scholar
[17]

Benson AB, D'Angelica MI, Abbott DE, et al. Hepatobiliary cancers, version 2.2021, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw 2021;19(5):541–65. https://doi.org/10.6004/jnccn.2021.0022.
Crossref Google Scholar
[18]

Petrick JL, Florio AA, Loomba R, et al. Have incidence rates of liver cancer peaked in the United States? Cancer 2020;126(13):3151–5. https://doi.org/10.1002/cncr.32794.
Crossref Google Scholar
[19]

McGlynn KA, Petrick JL, El-Serag HB. Epidemiology of hepatocellular carcinoma. Hepatology 2021;73(Suppl 1):4–13. https://doi.org/10.1002/hep.31288.
Crossref Google Scholar
[20]

Younossi ZM. Non-alcoholic fatty liver disease–A global public health perspective. J Hepatol 2019;70(3):531–44. https://doi.org/10.1016/j.jhep.2018.10.033.
Crossref Google Scholar
[21]

Younossi Z, Stepanova M, Ong JP, et al. Nonalcoholic steatohepatitis is the fastest growing cause of hepatocellular carcinoma in liver transplant candidates. Clin Gastroenterol Hepatol 2019;17(4):748. https://doi.org/10.1016/j.cgh.2018.05.057.55.e3.
Crossref Google Scholar
[22]

Brown ZJ, Tsilimigras DI, Ruff SM, et al. Management of hepatocellular carcinoma: a review. JAMA Surg 2023;158(4):410–20. https://doi.org/10.1001/jamasurg.2022.7989.
Crossref Google Scholar
[23]

Lee YB, Moon H, Lee JH, et al. Association of metabolic risk factors with risks of cancer and all-cause mortality in patients with chronic hepatitis B. Hepatology 2021;73(6):2266–77. https://doi.org/10.1002/hep.31612.
Crossref Google Scholar
[24]

Beal EW, Tumin D, Kabir A, et al. Trends in the mortality of hepatocellular carcinoma in the United States. J Gastrointest Surg 2017;21(12):2033–8. https://doi.org/10.1007/s11605-017-3526-7.
Crossref Google Scholar
[25]

Kobayashi T, Aikata H, Kobayashi T, et al. Patients with early recurrence of hepatocellular carcinoma have poor prognosis. Hepatobiliary Pancreat Dis Int 2017;16(3):279–88. https://doi.org/10.1016/s1499-3872(16)60181-9.
Crossref Google Scholar
[26]

Llovet JM, Pinyol R, Kelley RK, et al. Molecular pathogenesis and systemic therapies for hepatocellular carcinoma. Nat Can (Ott) 2022;3(4):386–401. https://doi.org/10.1038/s43018-022-00357-2.
Crossref Google Scholar
[27]

Cancer Genome Atlas Research Network. Electronic address: wheeler@bcm.edu, Cancer Genome Atlas Research Network. Comprehensive and integrative genomic characterization of hepatocellular carcinoma. Cell 2017;169(7):1327–41. https://doi.org/10.1016/j.cell.2017.05.046.
Crossref Google Scholar
[28]

Villanueva A, Portela A, Sayols S, et al. DNA methylation-based prognosis and epidrivers in hepatocellular carcinoma. Hepatology 2015;61(6):1945–56. https://doi.org/10.1002/hep.27732.
Crossref Google Scholar
[29]

Zou Q, Hou Y, Wang H, et al. Hydroxylase activity of ASPH promotes hepatocellular carcinoma metastasis through epithelial-to-mesenchymal transition pathway. EBioMedicine 2018;31:287–98. https://doi.org/10.1016/j.ebiom.2018.05.004.
Crossref Google Scholar
[30]

Llovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma. Nat Rev Dis Prim 2021;7(1):6. https://doi.org/10.1038/s41572-020-00240-3.
Crossref Google Scholar
[31]

Losic B, Craig AJ, Villacorta-Martin C, et al. Intratumoral heterogeneity and clonal evolution in liver cancer. Nat Commun 2020;11(1):291. https://doi.org/10.1038/s41467-019-14050-z.
Crossref Google Scholar
[32]

Heimbach JK, Kulik LM, Finn RS, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 2018;67(1):358–80. https://doi.org/10.1002/hep.29086.
Crossref Google Scholar
[33]

Kim DY, Toan BN, Tan CK, et al. Utility of combining PIVKA-Ⅱ and AFP in the surveillance and monitoring of hepatocellular carcinoma in the Asia-Pacific Region. Clin Mol Hepatol 2023;29(2):277–92. https://doi.org/10.3350/cmh.2022.0212.
Crossref Google Scholar
[34]

Xing H, Zheng YJ, Han J, et al. Protein induced by vitamin K absence or antagonist-Ⅱ versus alpha-fetoprotein in the diagnosis of hepatocellular carcinoma: a systematic review with meta-analysis. Hepatobiliary Pancreat Dis Int 2018;17(6):487–95. https://doi.org/10.1016/j.hbpd.2018.09.009.
Crossref Google Scholar
[35]

Wang MD, Sun LY, Qian GJ, et al. Prothrombin induced by vitamin K Absence-Ⅱ versus alpha-fetoprotein in detection of both resectable hepatocellular carcinoma and early recurrence after curative liver resection: a retrospective cohort study. Int J Surg 2022;105:106843. https://doi.org/10.1016/j.ijsu.2022.106843.
Crossref Google Scholar
[36]

Raoul JL, Forner A, Bolondi L, et al. Updated use of TACE for hepatocellular carcinoma treatment: how and when to use it based on clinical evidence. Cancer Treat Rev 2019;72:28–36. https://doi.org/10.1016/j.ctrv.2018.11.002.
Crossref Google Scholar
[37]

Llovet JM, De Baere T, Kulik L, et al. Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol 2021;18(5):293–313. https://doi.org/10.1038/s41575-020-00395-0.
Crossref Google Scholar
[38]

Raoul JL, Frenel JS, Raimbourg J, et al. Current options and future possibilities for the systemic treatment of hepatocellular carcinoma. Hepat Oncol 2019;6(1): HEP11. https://doi.org/10.2217/hep-2019-0001.
Crossref Google Scholar
[39]

Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med 2020;382(20):1894–905. https://doi.org/10.1056/NEJMoa1915745.
Crossref Google Scholar
[40]

Totoki Y, Tatsuno K, Covington KR, et al. Trans-ancestry mutational landscape of hepatocellular carcinoma genomes. Nat Genet 2014;46(12):1267–73. https://doi.org/10.1038/ng.3126.
Crossref Google Scholar
[41]

Ding XX, Zhu QG, Zhang SM, et al. Precision medicine for hepatocellular carcinoma: driver mutations and targeted therapy. Oncotarget 2017;8(33): 55715–30. https://doi.org/10.18632/oncotarget.18382.
Crossref Google Scholar
[42]

Hoshida Y, Villanueva A, Sangiovanni A, et al. Prognostic gene expression signature for patients with hepatitis C-related early-stage cirrhosis. Gastroenterology 2013;144(5):1024–30. https://doi.org/10.1053/j.gastro.2013.01.021.
Crossref Google Scholar
[43]

Calderaro J, Ziol M, Paradis V, et al. Molecular and histological correlations in liver cancer. J Hepatol 2019;71(3):616–30. https://doi.org/10.1016/j.jhep.2019.06.001.
Crossref Google Scholar
[44]

Chen VL, Xu D, Wicha MS, et al. Utility of liquid biopsy analysis in detection of hepatocellular carcinoma, determination of prognosis, and disease monitoring: a systematic review. Clin Gastroenterol Hepatol 2020;18(13):2879–2902.e9. https://doi.org/10.1016/j.cgh.2020.04.019.
Crossref Google Scholar
[45]

Ye Q, Ling S, Zheng S, et al. Liquid biopsy in hepatocellular carcinoma: circulating tumor cells and circulating tumor DNA. Mol Cancer 2019;18(1):114. https://doi.org/10.1186/s12943-019-1043-x.
Crossref Google Scholar
[46]

Kaseb AO, Sánchez NS, Sen S, et al. Molecular profiling of hepatocellular carcinoma using circulating cell-free DNA. Clin Cancer Res 2019;25(20):6107–18. https://doi.org/10.1158/1078-0432.CCR-18-3341.
Crossref Google Scholar
[47]

Harding-Theobald E, Louissaint J, Maraj B, et al. Systematic review: radiomics for the diagnosis and prognosis of hepatocellular carcinoma. Aliment Pharmacol Ther 2021;54(7):890–901. https://doi.org/10.1111/apt.16563.
Crossref Google Scholar
[48]

Lin D, Shen L, Luo M, et al. Circulating tumor cells: biology and clinical significance. Signal Transduct Targeted Ther 2021;6(1):404. https://doi.org/10.1038/s41392-021-00817-8.
Crossref Google Scholar
[49]

Vasseur A, Kiavue N, Bidard FC, et al. Clinical utility of circulating tumor cells: an update. Mol Oncol 2021;15(6):1647–66. https://doi.org/10.1002/1878-0261.12869.
Crossref Google Scholar
[50]

Deng Z, Wu S, Wang Y, et al. Circulating tumor cell isolation for cancer diagnosis and prognosis. EBioMedicine 2022;83:104237. https://doi.org/10.1016/j.ebiom.2022.104237.
Crossref Google Scholar
[51]

Ahn JC, Teng PC, Chen PJ, et al. Detection of circulating tumor cells and their implications as a biomarker for diagnosis, prognostication, and therapeutic monitoring in hepatocellular carcinoma. Hepatology 2021;73(1):422–36. https://doi.org/10.1002/hep.31165.
Crossref Google Scholar
[52]

Teng PC, Agopian VG, Lin TY, et al. Circulating tumor cells: a step toward precision medicine in hepatocellular carcinoma. J Gastroenterol Hepatol 2022; 37(7):1179–90. https://doi.org/10.1111/jgh.15886.
Crossref Google Scholar
[53]

Li CC, Yang HY, Mao YL. Research progress and prospects of circulating tumor cells in hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 2022;21(6): 514–5. https://doi.org/10.1016/j.hbpd.2022.07.001.
Crossref Google Scholar
[54]

Sun YF, Wu L, Liu SP, et al. Dissecting spatial heterogeneity and the immuneevasion mechanism of CTCs by single-cell RNA-seq in hepatocellular carcinoma. Nat Commun 2021;12(1):4091. https://doi.org/10.1038/s41467-021-24386-0.
Crossref Google Scholar
[55]

Dang DK, Park BH. Circulating tumor DNA: current challenges for clinical utility. J Clin Invest 2022;132(12):e154941. https://doi.org/10.1172/JCI154941.
Crossref Google Scholar
[56]

Moding EJ, Nabet BY, Alizadeh AA, et al. Detecting liquid remnants of solid tumors: circulating tumor DNA minimal residual disease. Cancer Discov 2021; 11(12):2968–86. https://doi.org/10.1158/2159-8290.CD-21-0634.
Crossref Google Scholar
[57]

Johnson P, Zhou Q, Dao DY, et al. Circulating biomarkers in the diagnosis and management of hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol 2022; 19(10):670–81. https://doi.org/10.1038/s41575-022-00620-y.
Crossref Google Scholar
[58]

Lyu X, Tsui YM, Ho DWH, et al. Liquid biopsy using cell-free or circulating tumor DNA in the management of hepatocellular carcinoma. Cell Mol Gastroenterol Hepatol 2022;13(6):1611–24. https://doi.org/10.1016/j.jcmgh.2022.02.008.
Crossref Google Scholar
[59]

Wu X, Li J, Gassa A, et al. Circulating tumor DNA as an emerging liquid biopsy biomarker for early diagnosis and therapeutic monitoring in hepatocellular carcinoma. Int J Biol Sci 2020;16(9):1551–62. https://doi.org/10.7150/ijbs.44024.
Crossref Google Scholar
[60]

Cai ZX, Chen G, Zeng YY, et al. Circulating tumor DNA profiling reveals clonal evolution and real-time disease progression in advanced hepatocellular carcinoma. Int J Cancer 2017;141(5):977–85. https://doi.org/10.1002/ijc.30798.
Crossref Google Scholar
[61]

van Niel G, D'Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol 2018;19(4):213–28. https://doi.org/10.1038/nrm.2017.125.
Crossref Google Scholar
[62]

Ortiz A. Extracellular vesicles in cancer progression. Semin Cancer Biol 2021;76: 139–42. https://doi.org/10.1016/j.semcancer.2021.05.032.
Crossref Google Scholar
[63]

Lee YT, Tran BV, Wang JJ, et al. The role of extracellular vesicles in disease progression and detection of hepatocellular carcinoma. Cancers 2021;13(12): 3076. https://doi.org/10.3390/cancers13123076.
Crossref Google Scholar
[64]

Nimitrungtawee N, Inmutto N, Chattipakorn SC, et al. Extracellular vesicles as a new hope for diagnosis and therapeutic intervention for hepatocellular carcinoma. Cancer Med 2021;10(23):8253–71. https://doi.org/10.1002/cam4.4370.
Crossref Google Scholar
[65]

Cabiati M, Salvadori C, Basta G, et al. miRNA and long non-coding RNA transcriptional expression in hepatocellular carcinoma cell line-secreted extracellular vesicles. Clin Exp Med 2022;22(2):245–55. https://doi.org/10.1007/s10238-021-00744-6.
Crossref Google Scholar
[66]

Liu D, Kang H, Gao M, et al. Exosome-transmitted circ_MMP2 promotes hepatocellular carcinoma metastasis by upregulating MMP2. Mol Oncol 2020; 14(6):1365–80. https://doi.org/10.1002/1878-0261.12637.
Crossref Google Scholar
[67]

Sun N, Zhang C, Lee YT, et al. HCC EV ECG score: an extracellular vesicle-based protein assay for detection of early-stage hepatocellular carcinoma. Hepatology 2023;77(3):774–88. https://doi.org/10.1002/hep.32692.
Crossref Google Scholar
[68]

Nuciforo S, Heim MH. Organoids to model liver disease. JHEP Rep 2021;3(1): 100198. https://doi.org/10.1016/j.jhepr.2020.100198.
Crossref Google Scholar
[69]

Dong R, Zhang B, Zhang X. Liver organoids: an in vitro 3D model for liver cancer study. Cell Biosci 2022;12(1):152. https://doi.org/10.1186/s13578-022-00890-8.
Crossref Google Scholar
[70]

Broutier L, Mastrogiovanni G, Verstegen MM, et al. Human primary liver cancerderived organoid cultures for disease modeling and drug screening. Nat Med 2017;23(12):1424–35. https://doi.org/10.1038/nm.4438.
Crossref Google Scholar
[71]

De Siervi S, Turato C. Liver organoids as an in vitro model to study primary liver cancer. Int J Mol Sci 2023;24(5):4529. https://doi.org/10.3390/ijms24054529.
Crossref Google Scholar
[72]

Calderaro J, Seraphin TP, Luedde T, et al. Artificial intelligence for the prevention and clinical management of hepatocellular carcinoma. J Hepatol 2022;76(6): 1348–61. https://doi.org/10.1016/j.jhep.2022.01.014.
Crossref Google Scholar
[73]

Nam D, Chapiro J, Paradis V, et al. Artificial intelligence in liver diseases: improving diagnostics, prognostics and response prediction. JHEP Rep 2022;4(4): 100443. https://doi.org/10.1016/j.jhepr.2022.100443.
Crossref Google Scholar
[74]

Wei J, Jiang H, Zhou Y, et al. Radiomics: a radiological evidence-based artificial intelligence technique to facilitate personalized precision medicine in hepatocellular carcinoma. Dig Liver Dis 2023;55(7):833–47. https://doi.org/10.1016/j.dld.2022.12.015.
Crossref Google Scholar
[75]

Fu Y, Wei X, Han Q, et al. Identification and characterization of a 25-lncRNA prognostic signature for early recurrence in hepatocellular carcinoma. BMC Cancer 2021;21(1):1165. https://doi.org/10.1186/s12885-021-08827-z.
Crossref Google Scholar
[76]

Desert R, Chen W, Ge X, et al. Hepatocellular carcinomas, exhibiting intratumor fibrosis, express cancer-specific extracellular matrix remodeling and WNT/TGFB signatures, associated with poor outcome. Hepatology 2023;78(3):741–57. https://doi.org/10.1097/HEP.0000000000000362.
Crossref Google Scholar
[77]

Peng X, Zhu J, Liu S, et al. Signature construction and molecular subtype identification based on cuproptosis-related genes to predict the prognosis and immune activity of patients with hepatocellular carcinoma. Front Immunol 2022; 13:990790. https://doi.org/10.3389/fimmu.2022.990790.
Crossref Google Scholar
[78]

Yang C, Huang X, Liu Z, et al. Metabolism-associated molecular classification of hepatocellular carcinoma. Mol Oncol 2020;14(4):896–913. https://doi.org/10.1002/1878-0261.12639.
Crossref Google Scholar
[79]

Shi Y, Wang J, Huang G, et al. A novel epithelial-mesenchymal transition gene signature for the immune status and prognosis of hepatocellular carcinoma. Hepatol Int 2022;16(4):906–17. https://doi.org/10.1007/s12072-022-10354-3.
Crossref Google Scholar
[80]

Shi Y, Huang G, Jiang F, et al. Deciphering a mitochondria-related signature to supervise prognosis and immunotherapy in hepatocellular carcinoma. Front Immunol 2022;13:1070593. https://doi.org/10.3389/fimmu.2022.1070593.
Crossref Google Scholar
[81]

Wang MD, Xiang H, Zhang L, et al. Integration of OV6 expression and CD68+ tumor-associated macrophages with clinical features better predicts the prognosis of patients with hepatocellular carcinoma. Transl Oncol 2022;25:101509. https://doi.org/10.1016/j.tranon.2022.101509.
Crossref Google Scholar
[82]

Liu Y, Wei X, Zhang X, et al. CT radiomics combined with clinical variables for predicting the overall survival of hepatocellular carcinoma patients after hepatectomy. Transl Oncol 2022;26:101536. https://doi.org/10.1016/j.tranon.2022.101536.
Crossref Google Scholar
[83]

Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359(4):378–90. https://doi.org/10.1056/nejmoa0708857.
Crossref Google Scholar
[84]

Kudo M, Finn RS, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 noninferiority trial. Lancet 2018;391(10126):1163–73. https://doi.org/10.1016/S0140-6736(18)30207-1.
Crossref Google Scholar
[85]

Kelley RK, Rimassa L, Cheng AL, et al. Cabozantinib plus atezolizumab versus sorafenib for advanced hepatocellular carcinoma (COSMIC-312):a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 2022;23(8):995–1008. https://doi.org/10.1016/S1470-2045(22)00326-6.
Crossref Google Scholar
[86]

Ochi H, Tani J, Tomonari T, et al. Sequential therapy including regorafenib for unresectable hepatocellular carcinoma: effect of early relative changes in hepatic functional reserve after regorafenib administration on prognosis. Hepatol Res 2021;51(12):1219–28. https://doi.org/10.1111/hepr.13713.
Crossref Google Scholar
[87]

Drilon A, Laetsch TW, Kummar S, et al. Efficacy of larotrectinib in TRK fusionpositive cancers in adults and children. N Engl J Med 2018;378(8):731–9. https://doi.org/10.1056/NEJMoa1714448.
Crossref Google Scholar
[88]

Lu X, Chen H, Patterson AV, et al. Fibroblast growth factor receptor 4 (FGFR4) selective inhibitors as hepatocellular carcinoma therapy: advances and prospects. J Med Chem 2019;62(6):2905–15. https://doi.org/10.1021/acs.jmedchem.8b01531.
Crossref Google Scholar
[89]

Liu JKH, Irvine AF, Jones RL, et al. Immunotherapies for hepatocellular carcinoma. Cancer Med 2022;11(3):571–91. https://doi.org/10.1002/cam4.4468.
Crossref Google Scholar
[90]

Yarchoan M, Xing D, Luan L, et al. Characterization of the immune microenvironment in hepatocellular carcinoma. Clin Cancer Res 2017;23(23): 7333–9. https://doi.org/10.1158/1078-0432.CCR-17-0950.
Crossref Google Scholar
[91]

El-Khoueiry AB, Sangro B, Yau T, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040):an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet 2017;389(10088): 2492–502. https://doi.org/10.1016/S0140-6736(17)31046-2.
Crossref Google Scholar
[92]

Finkelmeier F, Scheiner B, Leyh C, et al. Cabozantinib in advanced hepatocellular carcinoma: efficacy and safety data from an international multicenter real-life cohort. Liver Cancer 2021;10(4):360–9. https://doi.org/10.1159/000515490.
Crossref Google Scholar
[93]

Doebele RC, Drilon A, Paz-Ares L, et al. Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials. Lancet Oncol 2020;21(2):271–82. https://doi.org/10.1016/S1470-2045(19)30691-6.
Crossref Google Scholar
[94]

Hong DS, DuBois SG, Kummar S, et al. Larotrectinib in patients with TRK fusionpositive solid tumours: a pooled analysis of three phase 1/2 clinical trials. Lancet Oncol 2020;21(4):531–40. https://doi.org/10.1016/S1470-2045(19)30856-3.
Crossref Google Scholar
[95]

Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 2017;357(6349):409–13. https://doi.org/10.1126/science.aan6733.
Crossref Google Scholar
[96]

Zhao P, Li L, Jiang X, et al. Mismatch repair deficiency/microsatellite instability-high as a predictor for anti-PD-1/PD-L1 immunotherapy efficacy. J Hematol Oncol 2019;12(1):54. https://doi.org/10.1186/s13045-019-0738-1.
Crossref Google Scholar
[97]

Lin ZF, Qin LX, Chen JH. Biomarkers for response to immunotherapy in hepatobiliary malignancies. Hepatobiliary Pancreat Dis Int 2022;21(5):413–9. https://doi.org/10.1016/j.hbpd.2022.08.002.
Crossref Google Scholar
[98]

Zayac A, Almhanna K. Hepatobiliary cancers and immunotherapy: where are we now and where are we heading? Transl Gastroenterol Hepatol 2020;5:8. https://doi.org/10.21037/tgh.2019.09.07.
Crossref Google Scholar
[99]

Rezvani K, Rouce R, Liu E, et al. Engineering natural killer cells for cancer immunotherapy. Mol Ther 2017;25(8):1769–81. https://doi.org/10.1016/j.ymthe.2017.06.012.
Crossref Google Scholar
[100]

Gao Q, Dong X, Xu Q, et al. Therapeutic potential of CRISPR/Cas9 gene editing in engineered T-cell therapy. Cancer Med 2019;8(9):4254–64. https://doi.org/10.1002/cam4.2257.
Crossref Google Scholar
[101]

Shi D, Shi Y, Kaseb AO, et al. Chimeric antigen receptor-glypican-3 T-cell therapy for advanced hepatocellular carcinoma: results of phase Ⅰ trials. Clin Cancer Res 2020;26(15):3979–89. https://doi.org/10.1158/1078-0432.CCR-19-3259.
Crossref Google Scholar
[102]

Rezvani K, Rouce RH. The application of natural killer cell immunotherapy for the treatment of cancer. Front Immunol 2015;6:578. https://doi.org/10.3389/fimmu.2015.00578.
Crossref Google Scholar
[103]

Hao X, Sun G, Zhang Y, et al. Targeting immune cells in the tumor microenvironment of HCC: new opportunities and challenges. Front Cell Dev Biol 2021;9:775462. https://doi.org/10.3389/fcell.2021.775462.
Crossref Google Scholar
[104]

Kudo M. Scientific rationale for combined immunotherapy with PD-1/PD-L1 antibodies and VEGF inhibitors in advanced hepatocellular carcinoma. Cancers 2020;12(5):1089. https://doi.org/10.3390/cancers12051089.
Crossref Google Scholar
[105]

Kudo M, Han KH, Ye SL, et al. A changing paradigm for the treatment of intermediate-stage hepatocellular carcinoma: asia-pacific primary liver cancer expert consensus statements. Liver Cancer 2020;9(3):245–60. https://doi.org/10.1159/000507370.
Crossref Google Scholar
[106]

Kudo M. A new era in systemic therapy for hepatocellular carcinoma: atezolizumab plus bevacizumab combination therapy. Liver Cancer 2020;9(2): 119–37. https://doi.org/10.1159/000505189.
Crossref Google Scholar
[107]

Kelley RK, Sangro B, Harris W, et al. Safety, efficacy, and pharmacodynamics of tremelimumab plus durvalumab for patients with unresectable hepatocellular carcinoma: randomized expansion of a phase Ⅰ/Ⅱ study. J Clin Oncol 2021;39(27):2991–3001. https://doi.org/10.1200/JCO.20.03555.
Crossref Google Scholar
[108]

Lencioni R, Llovet JM, Han G, et al. Sorafenib or placebo plus TACE with doxorubicin-eluting beads for intermediate stage HCC: the SPACE trial. J Hepatol 2016;64(5):1090–8. https://doi.org/10.1016/j.jhep.2016.01.012.
Crossref Google Scholar
[109]

Chaudhary K, Poirion OB, Lu L, et al. Deep learning-based multi-omics integration robustly predicts survival in liver cancer. Clin Cancer Res 2018;24(6):1248–59. https://doi.org/10.1158/1078-0432.CCR-17-0853.
Crossref Google Scholar
[110]

Flaherty KT, Gray RJ, Chen AP, et al. Molecular landscape and actionable alterations in a genomically guided cancer clinical trial: national cancer institute molecular analysis for therapy choice (NCI-MATCH). J Clin Oncol 2020;38(33):3883–94. https://doi.org/10.1200/JCO.19.03010.
Crossref Google Scholar
[111]

Mangat PK, Halabi S, Bruinooge SS, et al. Rationale and design of the targeted agent and profiling utilization registry (TAPUR) study. JCO Precis Oncol 2018; 2018. https://doi.org/10.1200/PO.18.00122.
Crossref Google Scholar
iLIVER
Volume 3 Issue 1,
March 2024
DOI: 10.1016/j.iliver.2024.100083
Cite this article:
Wang M-D, Diao Y-K, Yao L-Q, et al. Emerging role of molecular diagnosis and personalized therapy for hepatocellular carcinoma. iLIVER, 2024, 3(1). https://doi.org/10.1016/j.iliver.2024.100083

271

Views

6

Crossref

5

Scopus

Altmetrics
Received: 10 December 2023
Revised: 06 January 2024
Accepted: 19 January 2024
Published: 09 February 2024
© 2024 The Authors. Tsinghua University Press.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Return