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Two-Dimensional (2D) Based Hybrid Polymeric Nanoparticles as Novel Potential Therapeutics in the Treatment of Hepatocellular Carcinoma

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Two-dimensional Hybrid Composites

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Abstract

Liver cancer, or primary hepatic malignancy, accounts for the sixth most common form of human cancer worldwide, and among this, 90% of liver cancer cases exhibit hepatocellular carcinoma (HCC). Due to several associated limitations, current drug-based therapies for treating HCC are insufficient for an effective and efficient approach. Combination therapies with two-dimensional (2D) hybrid nanomaterials enhance the performance of the biocompatible nanomaterials in HCC treatment. 2D hybrid nanomaterials delivered an effective potential in ablating tumours. Many researchers exploited the 2D hybrid nanomaterials in the treatment and diagnostic of various diseases including graphene oxide, reduced graphene oxide, transition metal dichalcogenides (MoS2, WS2, MoSe2, NbSe2, TiS2, ZrS2, TaS2, and WSe2), g-C3N4, transition metal oxides (TiO2 and MnO2), layered double hydroxides, hexagonal boron nitride, black phosphorus, boron nitride, bismuth selenide, and MXenes, but here we explored their potential in effective treatment of HCC. The market potential of nanomaterials is widely expanding due to their potential to overcome several limitations associated with pharmacological-based treatment approaches commercially available, including side effects, bioavailability, stability, and efficiency.

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References

  1. Global Burden of Disease Cancer Collaboration., Fitzmaurice, C., Allen, C., et al.: Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the global burden of disease study. JAMA Oncol. 3(4):524–548 (2017)

    Google Scholar 

  2. Llovet, J.M., Kelley, R.K., Villanueva, A., et al.: Hepatocellular carcinoma. Nat. Rev. Dis. Primers. 7(1), 6 (2021)

    Google Scholar 

  3. Yang, J., Pan, G., Guan, L., et al.: The burden of primary liver cancer caused by specific etiologies from 1990 to 2019 at the global, regional, and national levels. Cancer Med. 5, 1357–1370 (2022)

    Article  Google Scholar 

  4. Global Burden of Disease Liver Cancer Collaboration., Akinyemiju, T., Abera, S., et al.: The burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level: results from the global burden of disease study 2015. JAMA Oncol. 3(12), 1683–1691 (2017)

    Google Scholar 

  5. Kanwal, F., Kramer, J., Asch, S.M., et al.: Risk of hepatocellular cancer in HCV patients treated with direct-acting antiviral agents. Gastroenterology 153(4), 996-1005.e1 (2017)

    Article  Google Scholar 

  6. Estes, C., Razavi, H., Loomba, R., et al.: Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology 67(1), 123–133 (2018)

    Article  Google Scholar 

  7. Nishida, N.: Metabolic disease as a risk of hepatocellular carcinoma. Clin. Mol. Hepatol. 27(1), 87–90 (2021)

    Article  Google Scholar 

  8. Ascha, M.S., Hanouneh, I.A., Lopez, R., et al.: The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology 51(6), 1972–1978 (2010)

    Article  Google Scholar 

  9. Zhao, L.: The gut microbiota and obesity: from correlation to causality. Nat. Rev. Microbiol. 11(9), 639–647 (2013)

    Article  Google Scholar 

  10. WHO. data visualization tools for exploring the global cancer burden in 2020. https://gco.iarc.fr/today/. (2020). Accessed 20 May 2023

  11. Kulik, L., El-Serag, H.B.: Epidemiology and management of hepatocellular carcinoma. Gastroenterology 156(2), 477-491.e1 (2015)

    Article  Google Scholar 

  12. Petrick, J.L., Florio, A.A., Znaor, A., et al.: International trends in hepatocellular carcinoma incidence, 1978–2012. Int. J. Cancer 147(2), 317–330 (2020)

    Article  Google Scholar 

  13. Zhang, C.H., Cheng, Y., Zhang, S., et al.: Changing epidemiology of hepatocellular carcinoma in Asia. Liver Int. 42, 2029–2041 (2022)

    Article  Google Scholar 

  14. Sung, H., Ferlay, J., Siegel, R.L., et al.: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71, 209–249 (2021)

    Article  Google Scholar 

  15. Ferlay, J., Colombet, M., Soerjomataram, I., et al.: Cancer statistics for the year 2020: an overview. Int. J. Cancer 149, 778–789 (2021)

    Article  Google Scholar 

  16. Tellapuri, S., Sutphin, P.D., Beg, M.S., et al.: Staging systems of hepatocellular carcinoma: a review. Indian J. Gastroenterol. 37(6), 481–491 (2018)

    Article  Google Scholar 

  17. Liu, L., Chen, H., Wang, M., et al.: Combination therapy of sorafenib and TACE for unresectable HCC: a systematic review and meta-analysis. PLoS ONE 9(3), e91124 (2014)

    Article  Google Scholar 

  18. Chidambaranathan-Reghupaty, S., Fisher, P.B., Sarkar, D.: Hepatocellular carcinoma (HCC): epidemiology, etiology and molecular classification. Adv. Cancer Res. 149, 1–61 (2021)

    Article  Google Scholar 

  19. Huang, A., Yang, X.R., Chung, W.Y., et al.: Targeted therapy for hepatocellular carcinoma. Signal Transduct. Target. Ther. 5(1), 146 (2020)

    Article  Google Scholar 

  20. Li, M., Zhang, W., Wang, B., et al.: Ligand-based targeted therapy: a novel strategy for hepatocellular carcinoma. Int. J. Nanomed. 11, 5645–5669 (2016)

    Article  Google Scholar 

  21. Zeng, M., Xiao, Y., Liu, J., et al.: Exploring two-dimensional materials toward the next-generation circuits: from monomer design to assembly control. Chem. Rev. 118(13), 6236–6296 (2018)

    Article  Google Scholar 

  22. Tao, W., Zhu, X., Yu, X., et al.: Black phosphorus nanosheets as a robust delivery platform for cancer theranostics. Adv Mater. (1) (2017). https://doi.org/10.1002/adma.201603276

  23. Lin, H., Chen, Y., Shi, J.: Insights into 2D MXenes for versatile biomedical applications: current advances and challenges ahead. Adv. Sci. (Weinh). 5(10) (2018)

    Google Scholar 

  24. Global Burden of Disease Cancer Collaboration; Fitzmaurice, C., Allen, C., et al.: Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the global burden of disease study. JAMA Oncol. 3(4), 524–548 (2017)

    Google Scholar 

  25. International Agency for Research on Cancer. GLOBOCAN 2018. IARC. https://gco.iarc.fr/today/online-analysis-map?v=2020&mode=population&mode_population=continents&population=900&populations=900&key=asr&sex=0&cancer=11&type=0&statistic=5&prevalence=0&population_groupearth&color_palette=default&map_scale=quantile&map_nb_colors=5&continent=0&rotate=%255B10%252C0%255D. Accessed 03 March 2023

  26. Global Burden of Disease Liver Cancer Collaboration, Akinyemiju, T., Abera, S., et al.: The burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level: results from the global burden of disease study 2015. JAMA Oncol. 3(12), 1683–1691 (2017)

    Google Scholar 

  27. Ascha, M.S., Hanouneh, I.A., Lopez, R., et al.: The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology. 51(6), 1972–8 (2010)

    Google Scholar 

  28. WHO. Data Visualization Tools for Exploring the Global Cancer Burden in 2020. https://gco.iarc.fr/today/ (2020). Accessed 20 Aug 2023

  29. Kulik, L., El-Serag, H.B.: Epidemiology and management of hepatocellular carcinoma. Gastroenterology 156(2), 477–491 (2019)

    Article  Google Scholar 

  30. Sung, H., Ferlay, J., Siegel, R.L., et al.: Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71, 209–49 (2021)

    Google Scholar 

  31. Liu, L., Chen, H., Wang, M., et al.: Combination therapy of sorafenib and TACE for unresectable HCC: a systematic review and meta-analysis. PLoS One 20, 9(3) (2014)

    Google Scholar 

  32. Llovet, J.M., Kelley, R.K., Villanueva, A., et al.:. Hepatocellular carcinoma. Nat. Rev. Dis. Primers. 7(1), 6 (2021). https://doi.org/10.1038/s41572-020-00240-3

  33. Sirohi, B., Shrikhande, S.V., Gaikwad, V., et al.: Indian Council of Medical Research consensus document on hepatocellular carcinoma. Indian J. Med. Res. 152, 468–474 (2020)

    Article  Google Scholar 

  34. Kulkarni, A.V., Fatima, S., Sharma, M., et al.: Lenvatinib for unresectable hepatocellular carcinoma: the frst Indian experience. GastroHep. 3, 407–408 (2021)

    Article  Google Scholar 

  35. Kumar, M., Kumar, R., Hissar, S.S., et al.: Risk factors analysis for hepatocellular carcinoma in patients with and without cirrhosis: a case-control study of 213 hepatocellular carcinoma patients from India. J. Gastroenterol. Hepatol. 22, 1104–1111 (2007)

    Article  Google Scholar 

  36. Paul, S.B., Chalamalasetty, S.B., Vishnubhatla, S., et al.: Clinical profle, etiology and therapeutic outcome in 324 hepatocellular carcinoma patients at a tertiary care center in India. Oncology 77, 162–171 (2009)

    Article  Google Scholar 

  37. Sood, A., Midha, V., Goyal, O., et al.: Profle of hepatocellular carcinoma in a tertiary care hospital in Punjab in Northern India. Indian J. Gastroenterol. 33, 35–40 (2014)

    Article  Google Scholar 

  38. David, D., Raghavendran, A., Goel, A., et al.: Risk factors for nonalcoholic fatty liver disease are common in patients with non-B non-C hepatocellular carcinoma in India. Indian J. Gastroenterol. 36, 373–379 (2017)

    Article  Google Scholar 

  39. Kumar, A., Acharya, S.K., Singh, S.P., et al.: Update of Indian national association for study of the liver consensus on prevention, diagnosis, and management of hepatocellular carcinoma in India: the Puri Ii recommendations. J. Clin. Exp. Hepatol. 2020, 43–80 (2019)

    Google Scholar 

  40. Koshy, A., Devadas, K., Panackel, C., et al.: Multi-center prospective survey of hepatocellular carcinoma in Kerala: More than 1,200 cases. Indian J. Gastroenterol. 42 (2023)

    Google Scholar 

  41. Krishan, S., Dhiman, R.K., Kalra, N., et al.: Joint consensus statement of the Indian National association for study of the liver and Indian radiological and imaging association for the diagnosis and imaging of hepatocellular carcinoma incorporating liver imaging reporting and data system. J. Clin. Exp. Hepatol. 9, 625–651 (2019)

    Article  Google Scholar 

  42. Tohra, S., Duseja, A., Taneja, S., et al.: Experience with changing etiology and nontransplant curative treatment modalities for hepatocellular carcinoma in a real-life setting-a retrospective descriptive analysis. J. Clin. Exp. Hepatol. 11, 682–690 (2021)

    Article  Google Scholar 

  43. Li, M., Zhang, W., Wang, B., et al.: Ligand-based targeted therapy: a novel strategy for hepatocellular carcinoma. Int. J. Nanomed. 11, 5645–5669 (2016). https://doi.org/10.2147/IJN.S115727

  44. Llovet, J.M., Castet, F., Heikenwalder, M., et al.: Immunotherapies for hepatocellular carcinoma. Nat. Rev. Clin. Oncol. 19(3), 151–172 (2022). https://doi.org/10.1038/s41571-021-00573-2

  45. Sia, D., Villanueva, A., Friedman, SL., et al.: Liver cancer cell of origin, molecular class, and effects on patient prognosis. Gastroenterology 152(4), 745–761 (2017). https://doi.org/10.1053/j.gastro.2016.11.048

  46. Zhu, W., Li, H., Luo, P.: Emerging 2D nanomaterials for multimodel theranostics of cancer. Front Bioeng Biotechnol. 9, 769178 (2021)

    Article  Google Scholar 

  47. Nafiujjaman, M., Nurunnabi, M., Lee, Y.K.: Photolumiscence high quantum yield graphene quantum dots for imaging guided photodynamic therapy. Drug Metab. Pharmacokinet. 1(32), S46 (2017)

    Article  Google Scholar 

  48. Nurunnabi, M., Nafiujjaman, M., Lee, S.J., et al.: Preparation of ultra-thin hexagonal boron nitride nanoplates for cancer cell imaging and neurotransmitter sensing. Chem. Commun. (Camb.) 52(36), 6146–6149 (2016)

    Article  Google Scholar 

  49. Khatun, Z., Nurunnabi, M., Nafiujjaman, M., et al.: A hyaluronic acid nanogel for photo-chemo theranostics of lung cancer with simultaneous light-responsive controlled release of doxorubicin. Nanoscale 7(24), 10680–10689 (2015)

    Article  Google Scholar 

  50. Ashfaq, M., Talreja, N, Chauhan, D., et al.: Two-dimensional (2D) hybrid nanomaterials for diagnosis and treatment of Cancer. J. Drug Deliv. Sci. Technol. 70, 103268 (2022)

    Google Scholar 

  51. Wang, S.B., Ma, Y.Y., Chen, X.Y., et al.: Ceramide-graphene oxide nanoparticles enhance cytotoxicity and decrease HCC xenograft development: a novel approach for targeted cancer therapy. Front. Pharmacol. 10, 69 (2019)

    Article  Google Scholar 

  52. Sosnowska, M., Kutwin, M., Strojny, B., et al.: Graphene oxide nanofilm and chicken embryo extract decrease the invasiveness of HepG2 liver cancer cells. Cancer Nano 12, 2 (2021)

    Article  Google Scholar 

  53. Wang, K., Ruan, J., Song, H., et al.: Biocompatibility of graphene oxide. Nanoscale Res. Lett. 6(8), 1–8 (2011)

    Google Scholar 

  54. Wang, Y., Shenouda, S., Baranwal, S., et al.: Integrin subunits alpha5 and alpha6 regulate cell cycle by modulating the chk1 and Rb/E2F pathways to affect breast cancer metastasis. Mol. Cancer 10(1), 1–11 (2011)

    Article  Google Scholar 

  55. Ouyang, R., Cao, P., Jia, P., et al.: Bistratal Au@Bi2S3 nanobones for excellent NIR-triggered/multimodal imaging-guided synergistic therapy for liver cancer. Bioact Mater. 6(2), 386–403 (2020)

    Google Scholar 

  56. Zhao, W., Li, J., Zhong, C., et al.: Green synthesis of gold nanoparticles from Dendrobium officinale and its anticancer effect on liver cancer. Drug Deliv. 28(1), 985–994 (2021)

    Article  Google Scholar 

  57. Li, B., Fu, Y., Xie, M., et al.: Gold-based nanoparticles realize photothermal and photodynamic synergistic treatment of liver cancer and improve the anaerobic tumor microenvironment under near-infrared light. Front Bioeng Biotechnol. 10, 957349 (2022)

    Google Scholar 

  58. Yadong, Z., Kandasamy, V., Fafu, D., et al.: Hyper-branched multifunctional carbon nanotubes carrier for targeted liver cancer therapy. Arab. J. Chem. 15(3), 103649 (2022)

    Google Scholar 

  59. Iancu, C., Mocan, L., Bele, C., et al.: Enhanced laser thermal ablation for the in vitro treatment of liver cancer by specific delivery of multiwalled carbon nanotubes functionalized with human serum albumin. Int. J. Nanomedicine 6, 129–141 (2011)

    Article  Google Scholar 

  60. Das, T., Chakraborty, S., Sarma, H.D., et al.: 166Ho-labeled hydroxyapatite particles: a possible agent for liver cancer therapy. Cancer Biother. Radiopharm. 24(1), 7–14 (2009)

    Google Scholar 

  61. Awwad, N.S., Saleh, K.A., Abbas, H.A., et al.: Induction apoptosis in liver cancer cells by altering natural hydroxyapatite to scavenge excess sodium without deactivate sodium-potassium pump. Mater. Res. Express 6, 055403 (2019)

    Google Scholar 

  62. Ying, X., Yihan, K., Jiawen, X., et al.: Doxorubicin intercalated copper diethyldithiocarbamate functionalized layered double hydroxide hybrid nanoparticles for targeted therapy of hepatocellular carcinoma. Biomater. Sci. 8, 897–911 (2020)

    Google Scholar 

  63. Lu, Y.F., Zhou, J.P., Zhou, Q.M., et al.: Ultra-thin layered double hydroxide-mediated photothermal therapy combine with asynchronous blockade of PD-L1 and NR2F6 inhibit hepatocellular carcinoma. J. Nanobiotechnol. 20, 351 (2022)

    Article  Google Scholar 

  64. Liao, K.H., Lin, Y.S., Macosko, C.W., Haynes, C.L.: Cytotoxicity of graphene oxide and graphene in human erythrocytes and skin fibroblasts. ACS Appl. Mater. Interfaces 3(7), 2607–2615 (2011). https://doi.org/10.1021/am200428v

    Article  Google Scholar 

  65. Jaworski, S., Sawosz, E., Kutwin, M., Wierzbicki, M., Hinzmann, M., Grodzik, M., Winnicka, A., Lipińska, L., Włodyga, K., Chwalibog, A.: In vitro and in vivo effects of graphene oxide and reduced graphene oxide on glioblastoma. Int. J. Nanomed. 25(10), 1585–1596 (2015). https://doi.org/10.2147/IJN.S77591

    Article  Google Scholar 

  66. Zhang, Y., Ali, S.F., Dervishi, E., Xu, Y., Li, Z., Casciano, D., Biris, A.S.: Cytotoxicity effects of graphene and single-wall carbon nanotubes in neural phaeochromocytoma-derived PC12 cells. ACS Nano 4(6), 3181–3186 (2010). https://doi.org/10.1021/nn1007176

    Article  Google Scholar 

  67. Teo, W.Z., Chng, E.L., Sofer, Z., Pumera, M.: Cytotoxicity of exfoliated transition-metal dichalcogenides (MoS2, WS2, and WSe2) is lower than that of graphene and its analogues. Chemistry 20(31), 9627–9632 (2014). https://doi.org/10.1002/chem.201402680

    Article  Google Scholar 

  68. Shafizadeh, N., Kakar, S.: Diagnosis of well-differentiated hepatocellular lesions: role of immunohistochemistry and other ancillary techniques. Adv Anat Pathol 18(6), 438–445 (2011). https://doi.org/10.1097/PAP.0b013e318234abb4

    Article  Google Scholar 

  69. Michalopoulos, G.K., Bhushan, B.: Liver regeneration: biological and pathological mechanisms and implications. Nat. Rev. Gastroenterol. Hepatol. 18, 40–55 (2021)

    Article  Google Scholar 

  70. Bruno, S., Herrera Sanchez, M.B., Chiabotto, G., Fonsato, V., Navarro-Tableros, V., Pasquino, C., Tapparo, M., Camussi, G.: Human liver stem cells: a liver-derived mesenchymal stromal cell-like population with pro-regenerative properties. Front Cell Dev Biol. 26(9), 644088 (2021). https://doi.org/10.3389/fcell.2021.644088

    Article  Google Scholar 

  71. Bayard, Q., Meunier, L., Peneau, C., Renault, V., Shinde, J., Nault, J.C., Mami, I., Couchy, G., Amaddeo, G., Tubacher, E., Bacq, D., Meyer, V., La Bella, T., Debaillon-Vesque, A., Bioulac-Sage, P., Seror, O., Blanc, J.F., Calderaro, J., Deleuze, J.F., Imbeaud, S., Zucman-Rossi, J., Letouzé, E.: Cyclin A2/E1 activation defines a hepatocellular carcinoma subclass with a rearrangement signature of replication stress. Nat. Commun. 9(1), 5235 (2018). https://doi.org/10.1038/s41467-018-07552-9

    Article  Google Scholar 

  72. Pfister, D., Núñez, N.G., Pinyol, R., Govaere, O., Pinter, M., Szydlowska, M., Gupta, R., Qiu, M., Deczkowska, A., Weiner, A., Müller, F., Sinha, A., Friebel, E., Engleitner, T., Lenggenhager, D., Moncsek, A., Heide, D., Stirm, K., Kosla, J., Kotsiliti, E., Leone, V., Dudek, M., Yousuf, S., Inverso, D., Singh, I., Teijeiro, A., Castet, F., Montironi, C., Haber, P.K., Tiniakos, D., Bedossa, P., Cockell, S., Younes, R., Vacca, M., Marra, F., Schattenberg, J.M., Allison, M., Bugianesi, E., Ratziu, V., Pressiani, T., D'Alessio, A., Personeni, N., Rimassa, L., Daly, A.K., Scheiner, B., Pomej, K., Kirstein, M.M., Vogel, A., Peck-Radosavljevic, M., Hucke, F., Finkelmeier, F., Waidmann, O., Trojan, J., Schulze, K., Wege, H., Koch, S., Weinmann, A., Bueter, M., Rössler, F., Siebenhüner, A., De Dosso, S., Mallm, J.P., Umansky, V., Jugold, M., Luedde, T., Schietinger, A., Schirmacher, P., Emu, B., Augustin, H.G., Billeter, A., Müller-Stich, B., Kikuchi, H., Duda, D.G., Kütting, F., Waldschmidt. D.T., Ebert, M.P., Rahbari, N., Mei, H.E., Schulz, A.R., Ringelhan, M., Malek, N., Spahn, S., Bitzer, M., Ruiz de Galarreta, M., Lujambio, A., Dufour, J.F., Marron, T.U., Kaseb, A., Kudo, M., Huang, Y.H., Djouder, N., Wolter, K., Zender, L., Marche, P.N., Decaens, T., Pinato, D.J., Rad, R., Mertens, J.C., Weber, A., Unger, K., Meissner, F., Roth, S., Jilkova, Z.M., Claassen, M., Anstee, Q.M., Amit, I., Knolle, P., Becher, B., Llovet, J.M., Heikenwalder, M.: NASH limits anti-tumour surveillance in immunotherapy-treated HCC. Nature 592(7854), 450–456 2021. https://doi.org/10.1038/s41586-021-03362-0

  73. Gellert-Kristensen, H., Richardson, T.G., Davey Smith, G., Nordestgaard, B.G., Tybjaerg-Hansen, A., Stender, S.: Combined effect of PNPLA3, TM6SF2, and HSD17B13 variants on risk of cirrhosis and hepatocellular carcinoma in the general population. Hepatology 72(3), 845–856 (2020). https://doi.org/10.1002/hep.31238

    Article  Google Scholar 

  74. Yang, J.D., Hainaut, P., Gores, G.J., Amadou, A., Plymoth, A., Roberts, L.R.: A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat. Rev. Gastroenterol. Hepatol. 16(10), 589–604 (2019). https://doi.org/10.1038/s41575-019-0186-y

    Article  Google Scholar 

  75. Nault, J.C., Letouzé, E.: Mutational processes in hepatocellular carcinoma: the story of aristolochic acid. Semin. Liver Dis. 39(3), 334–340 (2019). https://doi.org/10.1055/s-0039-1685516

    Article  Google Scholar 

  76. Guichard, C., Amaddeo, G., Imbeaud, S., Ladeiro, Y., Pelletier, L., Maad, I.B., Calderaro, J., Bioulac-Sage, P., Letexier, M., Degos, F., Clément, B., Balabaud, C., Chevet, E., Laurent, A., Couchy, G., Letouzé, E., Calvo, F., Zucman-Rossi, J.: Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma. Nat. Genet. 44(6), 694–698 (2012). https://doi.org/10.1038/ng.2256

    Article  Google Scholar 

  77. Takai, A., Dang, H.T., Wang, X.W.: Identification of drivers from cancer genome diversity in hepatocellular carcinoma. Int. J. Mol. Sci. 15(6), 11142–11160 (2014). https://doi.org/10.3390/ijms150611142

    Article  Google Scholar 

  78. Ahn, S.M., Jang, S.J., Shim, J.H., Kim, D., Hong, S.M., Sung, C.O., Baek, D., Haq, F., Ansari, A.A., Lee, S.Y., Chun, S.M., Choi, S., Choi, H.J., Kim, J., Kim, S., Hwang, S., Lee, Y.J., Lee, J.E., Jung, W.R., Jang, H.Y., Yang, E., Sung, W.K., Lee, N.P., Mao, M., Lee, C., Zucman-Rossi, J., Yu, E., Lee, H.C., Kong, G.: Genomic portrait of resectable hepatocellular carcinomas: implications of RB1 and FGF19 aberrations for patient stratification. Hepatology 60(6), 1972–1982 (2014). https://doi.org/10.1002/hep.27198

    Article  Google Scholar 

  79. Belinky, F., Nativ, N., Stelzer, G., Zimmerman, S., Iny Stein, T., Safran, M., Lancet, D.: PathCards: multi-source consolidation of human biological pathways. Database (Oxford). (2015) bav006

    Google Scholar 

  80. Schulze, K., Imbeaud, S., Letouzé, E., Alexandrov, L.B., Calderaro, J., Rebouissou, S., Couchy, G., Meiller, C., Shinde, J., Soysouvanh, F., Calatayud, A.L., Pinyol, R., Pelletier, L., Balabaud, C., Laurent, A., Blanc, J.F., Mazzaferro, V., Calvo, F., Villanueva, A., Nault, J.C., Bioulac-Sage, P., Stratton, M.R., Llovet, J.M., Zucman-Rossi, J.: Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets. Nat. Genet. 47(5), 505–511 (2015). https://doi.org/10.1038/ng.3252

    Article  Google Scholar 

  81. National Cancer Institute. The Cancer Genome Atlas. http://cancergenome.nih.gov/. Accessed 04 March 20

  82. Tao, J., Xu, E., Zhao, Y., Singh, S., Li, X., Couchy, G., Chen, X., Zucman-Rossi, J., Chikina, M., Monga, S.P.: Modeling a human hepatocellular carcinoma subset in mice through coexpression of met and point-mutant β-catenin. Hepatology 64(5), 1587–1605 (2016). https://doi.org/10.1002/hep.28601

    Article  Google Scholar 

  83. Ruiz de Galarreta, M., Bresnahan, E., Molina-Sánchez, P., Lindblad, KE., Maier, B., Sia, D., Puigvehi, M., Miguela, V., Casanova-Acebes, M., Dhainaut, M., Villacorta-Martin, C., Singhi, A.D., Moghe, A., von Felden, J., Tal Grinspan, L., Wang, S., Kamphorst, A.O., Monga, S.P., Brown, B.D., Villanueva, A., Llovet, J.M., Merad, M., Lujambio, A.: β-Catenin activation promotes immune escape and resistance to anti-PD-1 therapy in hepatocellular carcinoma. Cancer Discov. 9(8), 1124–1141 (2019). https://doi.org/10.1158/2159-8290.CD-19-0074

  84. Tao, J., Krutsenko, Y., Moghe, A., Singh, S., Poddar, M., Bell, A., Oertel, M., Singhi, A.D., Geller, D., Chen, X., Lujambio, A., Tan Liu, S., Monga, S.P.: Nuclear factor erythroid 2-related factor 2 and β-Catenin coactivation in hepatocellular cancer: biological and therapeutic implications. Hepatology 74(2), 741–759 (2021). https://doi.org/10.1002/hep.31730

    Article  Google Scholar 

  85. Tan, X., Behari, J., Cieply, B., Michalopoulos, G.K., Monga, S.P.: Conditional deletion of beta-catenin reveals its role in liver growth and regeneration. Gastroenterology 131(5), 1561–1572 (2006). https://doi.org/10.1053/j.gastro.2006.08.042

    Article  Google Scholar 

  86. Miyoshi, Y., Nagase, H., Ando, H., Horii, A., Ichii, S., Nakatsuru, S., Aoki, T., Miki, Y., Mori, T., Nakamura, Y.: Somatic mutations of the APC gene in colorectal tumors: mutation cluster region in the APC gene. Hum. Mol. Genet. 1(4), 229–233 (1992). https://doi.org/10.1093/hmg/1.4.229

    Article  Google Scholar 

  87. Li, J., Quan, H., Liu, Q., Si, Z., He, Z., Qi, H.: Alterations of axis inhibition protein 1 (AXIN1) in hepatitis B virus-related hepatocellular carcinoma and overexpression of AXIN1 induces apoptosis in hepatocellular cancer cells. Oncol. Res. 20(7), 281–288 (2013). https://doi.org/10.3727/096504013x13639794277608

    Article  Google Scholar 

  88. Satoh, S., Daigo, Y., Furukawa, Y., Kato, T., Miwa, N., Nishiwaki, T., Kawasoe, T., Ishiguro, H., Fujita, M., Tokino, T., Sasaki, Y., Imaoka, S., Murata, M., Shimano, T., Yamaoka, Y., Nakamura, Y.: AXIN1 mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of AXIN1. Nat. Genet. 24(3), 245–250 (2000). https://doi.org/10.1038/73448. PMID: 10700176

    Article  Google Scholar 

  89. Huang, S.M., Mishina, Y.M., Liu, S., Cheung, A., Stegmeier, F., Michaud, G.A., Charlat, O., Wiellette, E., Zhang, Y., Wiessner, S., Hild, M., Shi, X., Wilson, C.J., Mickanin, C., Myer, V., Fazal, A., Tomlinson, R., Serluca, F., Shao, W., Cheng, H., Shultz, M., Rau, C., Schirle, M., Schlegl, J., Ghidelli, S., Fawell, S., Lu, C., Curtis, D., Kirschner, M.W., Lengauer, C., Finan, P.M., Tallarico, J.A., Bouwmeester, T., Porter, J.A., Bauer, A., Cong, F.: Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature 461(7264), 614–620 (2009). https://doi.org/10.1038/nature08356

    Article  Google Scholar 

  90. Totoki, Y., Tatsuno, K., Covington, K.R., Ueda, H., Creighton, C.J., Kato, M., Tsuji, S., Donehower, L.A., Slagle, B.L., Nakamura, H., Yamamoto, S., Shinbrot, E., Hama, N., Lehmkuhl, M., Hosoda, F., Arai, Y., Walker, K., Dahdouli, M., Gotoh, K., Nagae, G., Gingras, M.C., Muzny, D.M., Ojima, H., Shimada, K., Midorikawa, Y., Goss, J.A., Cotton, R., Hayashi, A., Shibahara, J., Ishikawa, S., Guiteau, J., Tanaka, M., Urushidate, T., Ohashi, S., Okada, N., Doddapaneni, H., Wang, M., Zhu, Y., Dinh, H., Okusaka, T., Kokudo, N., Kosuge, T., Takayama, T., Fukayama, M., Gibbs, R.A., Wheeler, D.A., Aburatani, H., Shibata, T.: Trans-ancestry mutational landscape of hepatocellular carcinoma genomes. Nat. Genet. 46(12), 1267–1273 (2014). https://doi.org/10.1038/ng.3126

    Article  Google Scholar 

  91. Pezzuto, F., Izzo, F., Buonaguro, L., Annunziata, C., Tatangelo, F., Botti, G., Buonaguro, F.M., Tornesello, M.L.: Tumor specific mutations in TERT promoter and CTNNB1 gene in hepatitis B and hepatitis C related hepatocellular carcinoma. Oncotarget 7(34), 54253–54262 (2016). https://doi.org/10.18632/oncotarget.9801

    Article  Google Scholar 

  92. Huang, F.W., Hodis, E., Xu, M.J., Kryukov, G.V., Chin, L., Garraway, L.A.: Highly recurrent TERT promoter mutations in human melanoma. Science 339(6122), 957–959 (2013). https://doi.org/10.1126/science.1229259

    Article  Google Scholar 

  93. Horn, S., Figl, A., Rachakonda, P.S., Fischer, C., Sucker, A., Gast, A., Kadel, S., Moll, I., Nagore, E., Hemminki, K., Schadendorf, D., Kumar, R.: TERT promoter mutations in familial and sporadic melanoma. Science 339(6122), 959–961 (2013). https://doi.org/10.1126/science.1230062

    Article  Google Scholar 

  94. Borah, S., Xi, L., Zaug, A.J., Powell, N.M., Dancik, G.M., Cohen, S.B., Costello, J.C., Theodorescu, D., Cech, T.R.: Cancer. TERT promoter mutations and telomerase reactivation in urothelial Cancer. Science. 347(6225), 1006–10010 (2015). https://doi.org/10.1126/science.1260200

  95. Lombardo, D., Saitta, C., Giosa, D., Di Tocco, F.C., Musolino, C., Caminiti, G., Chines, V., Franzè, M.S., Alibrandi, A., Navarra, G., Raimondo, G., Pollicino, T.: Frequency of somatic mutations in TERT promoter, TP53 and CTNNB1 genes in patients with hepatocellular carcinoma from Southern Italy. Oncol. Lett. 19(3), 2368–2374 (2020). https://doi.org/10.3892/ol.2020.11332

    Article  Google Scholar 

  96. Sirma, H., Kumar, M., Meena, J.K., Witt, B., Weise, J.M., Lechel, A., Ande, S., Sakk, V., Guguen-Guillouzo, C., Zender, L., Rudolph, K.L., Günes, C.: The promoter of human telomerase reverse transcriptase is activated during liver regeneration and hepatocyte proliferation. Gastroenterology. 141(1), 326–37, 337.e1-3 2011. https://doi.org/10.1053/j.gastro.2011.03.047

  97. Liu, T., Li, W., Lu, W., Chen, M., Luo, M., Zhang, C., Li, Y., Qin, G., Shi, D., Xiao, B., Qiu, H., Yu, W., Kang, L., Kang, T., Huang, W., Yu, X., Wu, X., Deng, W.: RBFOX3 promotes tumor growth and progression via hTERT signaling and predicts a poor prognosis in hepatocellular carcinoma. Theranostics. 7(12), 3138–3154 (2017). https://doi.org/10.7150/thno.19506

    Article  Google Scholar 

  98. Esopi, D., Graham, M.K., Brosnan-Cashman, J.A., Meyers, J., Vaghasia, A., Gupta, A., Kumar, B., Haffner, M.C., Heaphy, C.M., De Marzo, A.M., Meeker, A.K., Nelson, W.G., Wheelan, S.J., Yegnasubramanian, S.: Pervasive promoter hypermethylation of silenced TERT alleles in human cancers. Cell. Oncol. (Dordr.) 43(5), 847–861 (2020). https://doi.org/10.1007/s13402-020-00531-7

    Article  Google Scholar 

  99. Montironi, C., Castet, F., Haber, P.K., Pinyol, R., Torres-Martin, M., Torrens, L., Mesropian, A., Wang, H., Puigvehi, M., Maeda, M., Leow, W.Q., Harrod, E., Taik, P., Chinburen, J., Taivanbaatar, E., Chinbold, E., Solé Arqués, M., Donovan, M., Thung, S., Neely, J., Mazzaferro, V., Anderson, J., Roayaie, S., Schwartz, M., Villanueva, A., Friedman, S.L., Uzilov, A., Sia, D., Llovet, J.M.: Inflamed and non-inflamed classes of HCC: a revised immunogenomic classification. Gut 72(1), 129–140 (2023). https://doi.org/10.1136/gutjnl-2021-325918

    Article  Google Scholar 

  100. Villanueva, A., Hoshida, Y.: Depicting the role of TP53 in hepatocellular carcinoma progression. J. Hepatol. 55(3), 724–725 (2011). https://doi.org/10.1016/j.jhep.2011.03.018

    Article  Google Scholar 

  101. Jeng, Y.M., Hsu, H.C.: Mutation of the DR5/TRAIL receptor 2 gene is infrequent in hepatocellular carcinoma. Cancer Lett. 181(2), 205–208 (2002). https://doi.org/10.1016/s0304-3835(02)00051-4

    Article  Google Scholar 

  102. Liu, S., Qiu, J., He, G., et al.: TRAIL promotes hepatocellular carcinoma apoptosis and inhibits proliferation and migration via interacting with IER3. Cancer Cell Int. 21, 63 (2021). https://doi.org/10.1186/s12935-020-01724-8

    Article  Google Scholar 

  103. Salmena, L., Lemmers, B., Hakem, A., Matysiak-Zablocki, E., Murakami, K., Au, P.Y., Berry, D.M., Tamblyn, L., Shehabeldin, A., Migon, E., Wakeham, A., Bouchard, D., Yeh, W.C., McGlade, J.C., Ohashi, P.S., Hakem, R.: Essential role for caspase 8 in T-cell homeostasis and T-cell-mediated immunity. Genes Dev. 17(7), 883–895 (2003). https://doi.org/10.1101/gad.1063703

    Article  Google Scholar 

  104. Kim, I.K., Chung, C.W., Woo, H.N., Hong, G.S., Nagata, S., Jung, Y.K.: Reconstitution of caspase-8 sensitizes JB6 cells to TRAIL. Biochem. Biophys. Res. Commun. 277(2), 311–316 (2000). https://doi.org/10.1006/bbrc.2000.3673

    Article  Google Scholar 

  105. Kischkel, F.C., Lawrence, D.A., Chuntharapai, A., Schow, P., Kim, K.J., Ashkenazi, A.: Apo2L/TRAIL-dependent recruitment of endogenous FADD and caspase-8 to death receptors 4 and 5. Immunity 12(6), 611–620 (2000). https://doi.org/10.1016/s1074-7613(00)80212-5

    Article  Google Scholar 

  106. Lin, Y., Devin, A., Cook, A., Keane, M.M., Kelliher, M., Lipkowitz, S., Liu, Z.G.: The death domain kinase RIP is essential for TRAIL (Apo2L)-induced activation of IkappaB kinase and c-Jun N-terminal kinase. Mol. Cell Biol. 20(18), 6638–6645 (2000). https://doi.org/10.1128/MCB.20.18.6638-6645.2000

    Article  Google Scholar 

  107. Schneider, P., Thome, M., Burns, K., Bodmer, J.L., Hofmann, K., Kataoka, T., Holler, N., Tschopp, J.: TRAIL receptors 1 (DR4) and 2 (DR5) signal FADD-dependent apoptosis and activate NF-kappaB. Immunity 7(6), 831–836 (1997). https://doi.org/10.1016/s1074-7613(00)80401-x

    Article  Google Scholar 

  108. Knudsen, E.S., Gopal, P., Singal, A.G.: The changing landscape of hepatocellular carcinoma: etiology, genetics, and therapy. Am. J. Pathol. 184(3), 574–583 (2014). https://doi.org/10.1016/j.ajpath.2013.10.028

    Article  Google Scholar 

  109. Llovet, J.M., Villanueva, A., Lachenmayer A, Finn, R.S.: Advances in targeted therapies for hepatocellular carcinoma in the genomic era. Nat. Rev. Clin. Oncol. 12(8), 436 (2015). https://doi.org/10.1038/nrclinonc.2015.121. Epub 2015 Jun 23. Erratum for: Nat. Rev. Clin. Oncol. (2015) 12(7), 408–24

  110. Sawey, E.T., Chanrion, M., Cai, C., Wu, G., Zhang, J., Zender, L., Zhao, A., Busuttil, R.W., Yee, H., Stein, L., French, D.M., Finn, R.S., Lowe, S.W., Powers, S.: Identification of a therapeutic strategy targeting amplified FGF19 in liver cancer by Oncogenomic screening. Cancer Cell 19(3), 347–358 (2011). https://doi.org/10.1016/j.ccr.2011.01.040

    Article  Google Scholar 

  111. Anstee, Q.M., Reeves, H.L., Kotsiliti, E., Govaere, O., Heikenwalder, M.: From NASH to HCC: current concepts and future challenges. Nat. Rev. Gastroenterol. Hepatol. 16(7), 411–428 (2019). https://doi.org/10.1038/s41575-019-0145-7

    Article  Google Scholar 

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Raghav, A., Goo-Bo-Jeong (2024). Two-Dimensional (2D) Based Hybrid Polymeric Nanoparticles as Novel Potential Therapeutics in the Treatment of Hepatocellular Carcinoma. In: Talreja, N., Chauhan, D., Ashfaq, M. (eds) Two-dimensional Hybrid Composites. Engineering Materials. Springer, Singapore. https://doi.org/10.1007/978-981-99-8010-9_12

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