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Current Cancer Drug Targets

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Review Article

Resistance of Lenvatinib in Hepatocellular Carcinoma

Author(s): Jinhui Guo, Junjun Zhao, Qiuran Xu* and Dongsheng Huang*

Volume 22, Issue 11, 2022

Published on: 18 August, 2022

Page: [865 - 878] Pages: 14

DOI: 10.2174/1568009622666220428111327

Price: $65

Abstract

Lenvatinib is a multikinase inhibitor which mainly hinders liver cancer proliferation by inhibiting angiogenesis. In 2018, Lenvatinib was approved for the first-line treatment of patients with advanced hepatocellular carcinoma [HCC] in the United States, the European Union, Japan, and China. Lenvatinib has been established as a sorafenib replacement drug with a higher objective response rate [ORR], longer progression-free survival [PFS], and time to progression [TTP]. Lenvatinib resistance during hepatocellular carcinoma treatment has become increasingly common in recent years. Accordingly, it is necessary to determine factors associated with Lenvatinib resistance and explore solutions. In this review, we sought to explore the drug resistance mechanisms of Lenvatinib in liver cancer and methods to reduce drug resistance and summarized the recent achievements of Lenvatinib in liver cancer treatment.

Keywords: Lenvatinib, hepatocellular carcinoma, drug resistance, immune checkpoint inhibitor, systemic therapy, mechanism.

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[1]
Deng, S.; Solinas, A.; Calvisi, D.F. Cabozantinib for HCC treatment, from clinical back to experimental models. Front. Oncol., 2021, 11, 756672.
[http://dx.doi.org/10.3389/fonc.2021.756672] [PMID: 34722310]
[2]
Asafo-Agyei, K.O.; Samant, H. Pregnancy and viral hepatitis; StatPearls Publishing: Treasure Island, FL, 2022.
[3]
Zhao, P.; Malik, S.; Xing, S. Epigenetic mechanisms involved in HCV-induced hepatocellular carcinoma (HCC). Front. Oncol., 2021, 11, 677926.
[http://dx.doi.org/10.3389/fonc.2021.677926] [PMID: 34336665]
[4]
Marrero, J.A.; Kulik, L.M.; Sirlin, C.B.; Zhu, A.X.; Finn, R.S.; Abecassis, M.M. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of liver diseases. Hepatology, 2018, 68(2), 723-750.
[5]
Rich, N.E.; Parikh, N.D.; Singal, A.G. Hepatocellular carcinoma and liver transplantation: Changing patterns and practices. Curr. Treat. Options Gastroenterol., 2017, 15(2), 296-304.
[http://dx.doi.org/10.1007/s11938-017-0133-3] [PMID: 28425018]
[6]
Nault, J.C.; Ningarhari, M. The role of telomeres and telomerase in cirrhosis and liver cancer. Nat. Rev. Gastroenterol. Hepatol., 2019, 16(9), 544-558.
[http://dx.doi.org/10.1038/s41575-019-0165-3]
[7]
Calderaro, J.; Ziol, M.; Paradis, V.; Zucman-Rossi, J. Molecular and histological correlations in liver cancer. J. Hepatol., 2019, 71(3), 616-630.
[http://dx.doi.org/10.1016/j.jhep.2019.06.001] [PMID: 31195064]
[8]
Kanwal, F.; Singal, A.G. Surveillance for hepatocellular carcinoma: Current best practice and future direction. Gastroenterology, 2019, 157(1), 54-64.
[http://dx.doi.org/10.1053/j.gastro.2019.02.049] [PMID: 30986389]
[9]
Wang, C.I.; Chu, P.M.; Chen, Y.L.; Lin, Y.H. Chemotherapeutic drug-regulated cytokines might influence therapeutic efficacy in HCC. Int. J. Mol. Sci., 2021, 22(24), 13627.
[http://dx.doi.org/10.3390/ijms222413627]
[10]
Hao, X.; Sun, G.; Zhang, Y.; Kong, X.; Rong, D.; Song, J.; Tang, W.; Wang, X. Targeting immune cells in the tumor microenvironment of HCC: New opportunities and challenges. Front. Cell Dev. Biol., 2021, 9, 775462.
[http://dx.doi.org/10.3389/fcell.2021.775462] [PMID: 34869376]
[11]
Zhu, Y.J.; Zheng, B.; Wang, H.Y.; Chen, L. New knowledge of the mechanisms of sorafenib resistance in liver cancer. Acta Pharmacol. Sin., 2017, 38(5), 614-622.
[http://dx.doi.org/10.1038/aps.2017.5] [PMID: 28344323]
[12]
Cheng, A.L.; Kang, Y.K.; Lin, D.Y.; Park, J.W.; Kudo, M.; Qin, S.; Chung, H.C.; Song, X.; Xu, J.; Poggi, G.; Omata, M.; Pitman Lowenthal, S.; Lanzalone, S.; Yang, L.; Lechuga, M.J.; Raymond, E. Sunitinib versus sorafenib in advanced hepatocellular cancer: Results of a randomized phase III trial. J. Clin. Oncol., 2013, 31(32), 4067-4075.
[http://dx.doi.org/10.1200/JCO.2012.45.8372] [PMID: 24081937]
[13]
Johnson, P.J.; Qin, S.; Park, J.W.; Poon, R.T.; Raoul, J.L.; Philip, P.A.; Hsu, C.H.; Hu, T.H.; Heo, J.; Xu, J.; Lu, L.; Chao, Y.; Boucher, E.; Han, K.H.; Paik, S.W.; Robles-Aviña, J.; Kudo, M.; Yan, L.; Sobhonslidsuk, A.; Komov, D.; Decaens, T.; Tak, W.Y.; Jeng, L.B.; Liu, D.; Ezzeddine, R.; Walters, I.; Cheng, A.L. Brivanib versus sorafenib as first-line therapy in patients with unresectable, advanced hepatocellular carcinoma: Results from the randomized phase III BRISK-FL study. J. Clin. Oncol., 2013, 31(28), 3517-3524.
[http://dx.doi.org/10.1200/JCO.2012.48.4410] [PMID: 23980084]
[14]
Llovet, J.M.; Hernandez-Gea, V. Hepatocellular carcinoma: Reasons for phase III failure and novel perspectives on trial design. Clin. Cancer Res., 2014, 20(8), 2072-2079.
[http://dx.doi.org/10.1158/1078-0432.CCR-13-0547] [PMID: 24589894]
[15]
Rehman, O.; Jaferi, U.; Padda, I.; Khehra, N.; Atwal, H.; Mossabeh, D.; Bhangu, R. Overview of lenvatinib as a targeted therapy for advanced hepatocellular carcinoma. Clin. Exp. Hepatol., 2021, 7(3), 249-257.
[http://dx.doi.org/10.5114/ceh.2021.109312] [PMID: 34712825]
[16]
Rimassa, L.; Pressiani, T.; Merle, P. Systemic treatment options in hepatocellular carcinoma. Liver Cancer, 2019, 8(6), 427-446.
[http://dx.doi.org/10.1159/000499765] [PMID: 31799201]
[17]
Kim, JJ; McFarlane, T; Tully, S Wong, WWL Lenvatinib versus Sorafenib as first-line treatment of unresectable hepatocellular carcinoma: A cost-utility analysis. The Oncologist, 2020, 25(3), e512-e519.
[http://dx.doi.org/10.1634/theoncologist.2019-0501]
[18]
Jin, H; Shi, Y; Lv, Y; Yuan, S; Ramirez, CFA; Lieftink, C EGFR activation limits the response of liver cancer to lenvatinib. Nature, 2021, 595(7869), 730-734.
[http://dx.doi.org/10.1038/s41586-021-03741-7]
[19]
Yi, C.; Chen, L. Lenvatinib targets FGF receptor 4 to enhance antitumor immune response of anti-programmed cell death-1 in HCC. Hepatology, 2021, 74(5), 2544-2560.
[http://dx.doi.org/10.1002/hep.31921]
[20]
Okamoto, K.; Ikemori-Kawada, M.; Jestel, A.; von König, K.; Funahashi, Y.; Matsushima, T.; Tsuruoka, A.; Inoue, A.; Matsui, J. Distinct binding mode of multikinase inhibitor lenvatinib revealed by biochemical characterization. ACS Med. Chem. Lett., 2014, 6(1), 89-94.
[http://dx.doi.org/10.1021/ml500394m] [PMID: 25589937]
[21]
Yamamoto, Y.; Matsui, J.; Matsushima, T.; Obaishi, H.; Miyazaki, K.; Nakamura, K.; Tohyama, O.; Semba, T.; Yamaguchi, A.; Hoshi, S.S.; Mimura, F.; Haneda, T.; Fukuda, Y.; Kamata, J.I.; Takahashi, K.; Matsukura, M.; Wakabayashi, T.; Asada, M.; Nomoto, K.I.; Watanabe, T.; Dezso, Z.; Yoshimatsu, K.; Funahashi, Y.; Tsuruoka, A. Lenvatinib, an angiogenesis inhibitor targeting VEGFR/FGFR, shows broad antitumor activity in human tumor xenograft models associated with microvessel density and pericyte coverage. Vasc. Cell, 2014, 6(1), 18.
[http://dx.doi.org/10.1186/2045-824X-6-18] [PMID: 25197551]
[22]
Shigesawa, T.; Maehara, O.; Suda, G.; Natsuizaka, M.; Kimura, M.; Shimazaki, T.; Yamamoto, K.; Yamada, R.; Kitagataya, T.; Nakamura, A.; Suzuki, K.; Ohara, M.; Kawagishi, N.; Umemura, M.; Nakai, M.; Sho, T.; Morikawa, K.; Ogawa, K.; Ohnishi, S.; Sugiyama, M.; Mizo-kami, M.; Takeda, H.; Sakamoto, N. Lenvatinib suppresses cancer stem-like cells in HCC by inhibiting FGFR1-3 signaling, but not FGFR4 signaling. Carcinogenesis, 2021, 42(1), 58-69.
[http://dx.doi.org/10.1093/carcin/bgaa049] [PMID: 32449510]
[23]
Ornitz, D.M.; Itoh, N. The fibroblast growth factor signaling pathway. Wiley Interdiscip. Rev. Dev. Biol., 2015, 4(3), 215-266.
[http://dx.doi.org/10.1002/wdev.176] [PMID: 25772309]
[24]
Ikeda, M.; Okusaka, T.; Mitsunaga, S.; Ueno, H.; Tamai, T.; Suzuki, T.; Hayato, S.; Kadowaki, T.; Okita, K.; Kumada, H. Safety and pharmacokinetics of lenvatinib in patients with advanced hepatocellular carcinoma. Clin. Cancer Res., 2016, 22(6), 1385-1394.
[http://dx.doi.org/10.1158/1078-0432.CCR-15-1354] [PMID: 26500236]
[25]
Torrens, L.; Montironi, C. Immunomodulatory effects of lenvatinib plus anti-programmed cell death protein 1 in mice and rationale for patient enrichment in hepatocellular carcinoma. Hepatology, 2021, 74(5), 2652-2669.
[http://dx.doi.org/10.1002/hep.32023]
[26]
Voron, T.; Colussi, O.; Marcheteau, E.; Pernot, S.; Nizard, M.; Pointet, A.L.; Latreche, S.; Bergaya, S.; Benhamouda, N.; Tanchot, C.; Stockmann, C.; Combe, P.; Berger, A.; Zinzindohoue, F.; Yagita, H.; Tartour, E.; Taieb, J.; Terme, M. VEGF-A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors. J. Exp. Med., 2015, 212(2), 139-148.
[http://dx.doi.org/10.1084/jem.20140559] [PMID: 25601652]
[27]
He, Y.; Luo, Y.; Huang, L.; Zhang, D.; Wang, X.; Ji, J.; Liang, S. New frontiers against sorafenib resistance in renal cell carcinoma: From molecular mechanisms to predictive biomarkers. Pharmacol. Res., 2021, 170, 105732.
[http://dx.doi.org/10.1016/j.phrs.2021.105732] [PMID: 34139345]
[28]
Hu, X.; Zhu, H.; Shen, Y.; Zhang, X.; He, X.; Xu, X. The role of non-coding RNAs in the sorafenib resistance of hepatocellular carcinoma. Front. Oncol., 2021, 11, 696705.
[http://dx.doi.org/10.3389/fonc.2021.696705] [PMID: 34367979]
[29]
Zeng, Z.; Lu, Q.; Liu, Y.; Zhao, J.; Zhang, Q.; Hu, L.; Shi, Z.; Tu, Y.; Xiao, Z.; Xu, Q.; Huang, D. Effect of the hypoxia inducible factor on sorafenib resistance of hepatocellular carcinoma. Front. Oncol., 2021, 11, 641522.
[http://dx.doi.org/10.3389/fonc.2021.641522] [PMID: 34307125]
[30]
Lee, Y.S.; Kim, S.M.; Kim, B.W.; Chang, H.J.; Kim, S.Y.; Park, C.S.; Park, K.C.; Chang, H.S. Anti-cancer effects of HNHA and lenvatinib by the suppression of EMT-mediated drug resistance in cancer stem cells. Neoplasia, 2018, 20(2), 197-206.
[http://dx.doi.org/10.1016/j.neo.2017.12.003] [PMID: 29331886]
[31]
Kudo, M.; Finn, R.S.; Qin, S.; Han, K.H.; Ikeda, K.; Piscaglia, F.; Baron, A.; Park, J.W.; Han, G.; Jassem, J.; Blanc, J.F.; Vogel, A.; Komov, D.; Evans, T.R.J.; Lopez, C.; Dutcus, C.; Guo, M.; Saito, K.; Kraljevic, S.; Tamai, T.; Ren, M.; Cheng, A.L. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: A randomised phase 3 non-inferiority trial. Lancet, 2018, 391(10126), 1163-1173.
[http://dx.doi.org/10.1016/S0140-6736(18)30207-1] [PMID: 29433850]
[32]
Serrano-Gomez, S.J.; Maziveyi, M.; Alahari, S.K. Regulation of epithelial-mesenchymal transition through epigenetic and post-translational modifications. Mol. Cancer, 2016, 15(1), 18.
[http://dx.doi.org/10.1186/s12943-016-0502-x] [PMID: 26905733]
[33]
Sueta, D.; Suyama, K.; Sueta, A.; Tabata, N.; Yamashita, T.; Tomiguchi, M.; Takeshita, T.; Yamamoto-Ibusuki, M.; Yamamoto, E.; Izumiya, Y.; Kaikita, K.; Yamamoto, Y.; Hokimoto, S.; Iwase, H.; Tsujita, K. Lenvatinib, an oral multi-kinases inhibitor, -associated hypertension: Potential role of vascular endothelial dysfunction. Atherosclerosis, 2017, 260, 116-120.
[http://dx.doi.org/10.1016/j.atherosclerosis.2017.03.039] [PMID: 28390289]
[34]
Pinter, M.; Peck-Radosavljevic, M. Review article: Systemic treatment of hepatocellular carcinoma. Aliment. Pharmacol. Ther., 2018, 48(6), 598-609.
[http://dx.doi.org/10.1111/apt.14913] [PMID: 30039640]
[35]
Kobayashi, M.; Kudo, M.; Izumi, N.; Kaneko, S.; Azuma, M.; Copher, R.; Meier, G.; Pan, J.; Ishii, M.; Ikeda, S. Cost-effectiveness analysis of lenvatinib treatment for patients with unresectable hepatocellular carcinoma (uHCC) compared with sorafenib in Japan. J. Gastroenterol., 2019, 54(6), 558-570.
[http://dx.doi.org/10.1007/s00535-019-01554-0] [PMID: 30788569]
[36]
Catalano, M.; Casadei-Gardini, A.; Vannini, G.; Campani, C.; Marra, F.; Mini, E.; Roviello, G. Lenvatinib: Established and promising drug for the treatment of advanced hepatocellular carcinoma. Expert Rev. Clin. Pharmacol., 2021, 14(11), 1353-1365.
[http://dx.doi.org/10.1080/17512433.2021.1958674] [PMID: 34289756]
[37]
Xu, K.; Wu, C.L.; Wang, Z.X. VEGF family gene expression as prognostic biomarkers for Alzheimer’s Disease and primary liver cancer. Comput. Math. Methods Med., 2021, 2021, 3422393.
[38]
Secker, G.A.; Harvey, N.L. Regulation of VEGFR signalling in lymphatic vascular development and disease: An update. Int. J. Mol. Sci., 2021, 22(14), 7760.
[http://dx.doi.org/10.3390/ijms22147760] [PMID: 34299378]
[39]
Lu, Y.; Shen, H.; Huang, W.; He, S.; Chen, J.; Zhang, D. Genome-scale CRISPR-Cas9 knockout screening in hepatocellular carcinoma with lenvatinib resistance. Cell Death Discov., 2021, 7(1), 359.
[http://dx.doi.org/10.1038/s41420-021-00747-y]
[40]
Ichikawa, K.; Miyano, S.W.; Adachi, Y.; Yamamoto, Y.; Matsui, J. Abstract 1374: Lenvatinib, tri-specific targeted therapy to VEGFR/FGFR/RET, suppresses angiogenesis through the inhibition of both VEGFR and FGFR signaling pathways. Cancer Res., 2015, 75(15), 1374.
[41]
Ogasawara, S.; Mihara, Y.; Kondo, R.; Kusano, H.; Akiba, J.; Yano, H. Antiproliferative effect of lenvatinib on human liver cancer cell lines in vitro and in vivo. Anticancer Res., 2019, 39(11), 5973-5982.
[http://dx.doi.org/10.21873/anticanres.13802] [PMID: 31704822]
[42]
Zhao, Z.; Zhang, D.; Wu, F.; Tu, J.; Song, J.; Xu, M. Sophoridine suppresses lenvatinib-resistant hepatocellular carcinoma growth by inhibiting RAS/MEK/ERK axis via decreasing VEGFR2 expression. J. Cell. Mol. Med., 2021, 25(1), 549-560.
[43]
Drusbosky, L.M.; Rodriguez, E.; Dawar, R.; Ikpeazu, C.V. Therapeutic strategies in RET gene rearranged non-small cell lung cancer. J. Hematol. Oncol., 2021, 14(1), 50.
[http://dx.doi.org/10.1186/s13045-021-01063-9]
[44]
Drilon, A.; Hu, Z.I.; Lai, G.G.Y.; Tan, D.S.W. Targeting RET-driven cancers: Lessons from evolving preclinical and clinical landscapes. Nat. Rev. Clin. Oncol., 2018, 15(3), 151-167.
[http://dx.doi.org/10.1038/nrclinonc.2017.175] [PMID: 29134959]
[45]
Nelson-Taylor, S.K.; Le, A.T.; Yoo, M.; Schubert, L.; Mishall, K.M.; Doak, A.; Varella-Garcia, M.; Tan, A.C.; Doebele, R.C. Resistance to RET-inhibition in RET-rearranged NSCLC is mediated by reactivation of RAS/MAPK signaling. Mol. Cancer Ther., 2017, 16(8), 1623-1633.
[http://dx.doi.org/10.1158/1535-7163.MCT-17-0008] [PMID: 28500237]
[46]
King, G.; Javle, M. FGFR inhibitors: Clinical activity and development in the treatment of cholangiocarcinoma. Curr. Oncol. Rep., 2021, 23(9), 108.
[http://dx.doi.org/10.1007/s11912-021-01100-3] [PMID: 34269915]
[47]
Goyal, L.; Kongpetch, S.; Crolley, V.E.; Bridgewater, J. Targeting FGFR inhibition in cholangiocarcinoma. Cancer Treat. Rev., 2021, 95, 102170.
[http://dx.doi.org/10.1016/j.ctrv.2021.102170] [PMID: 33735689]
[48]
Liu, G; Chen, T; Ding, Z; Wang, Y; Wei, Y; Wei, X. Inhibition of FGF-FGFR and VEGF-VEGFR signalling in cancer treatment., 2021, 54(4), e13009.
[http://dx.doi.org/10.1111/cpr.13009]
[49]
Matsuki, M.; Hoshi, T.; Yamamoto, Y.; Ikemori-Kawada, M.; Minoshima, Y.; Funahashi, Y.; Matsui, J. Lenvatinib inhibits angiogenesis and tumor fibroblast growth factor signaling pathways in human hepatocellular carcinoma models. Cancer Med., 2018, 7(6), 2641-2653.
[http://dx.doi.org/10.1002/cam4.1517] [PMID: 29733511]
[50]
Tovar, V.; Cornella, H.; Moeini, A.; Vidal, S.; Hoshida, Y.; Sia, D.; Peix, J.; Cabellos, L.; Alsinet, C.; Torrecilla, S.; Martinez-Quetglas, I.; Lozano, J.J.; Desbois-Mouthon, C.; Solé, M.; Domingo-Domenech, J.; Villanueva, A.; Llovet, J.M. Tumour initiating cells and IGF/FGF signalling contribute to sorafenib resistance in hepatocellular carcinoma. Gut, 2017, 66(3), 530-540.
[http://dx.doi.org/10.1136/gutjnl-2015-309501] [PMID: 26658144]
[51]
Byron, S.A.; Chen, H.; Wortmann, A.; Loch, D.; Gartside, M.G.; Dehkhoda, F.; Blais, S.P.; Neubert, T.A.; Mohammadi, M.; Pollock, P.M. The N550K/H mutations in FGFR2 confer differential resistance to PD173074, dovitinib, and ponatinib ATP-competitive inhibitors. Neoplasia, 2013, 15(8), 975-988.
[http://dx.doi.org/10.1593/neo.121106] [PMID: 23908597]
[52]
Zhao, Z.; Song, J.; Zhang, D.; Wu, F.; Tu, J.; Ji, J. Oxysophocarpine suppresses FGFR1-overexpressed hepatocellular carcinoma growth and sensitizes the therapeutic effect of lenvatinib. Life Sci., 2021, 264, 118642.
[http://dx.doi.org/10.1016/j.lfs.2020.118642] [PMID: 33148422]
[53]
Babina, I.S.; Turner, N.C. Advances and challenges in targeting FGFR signalling in cancer. Nat. Rev. Cancer, 2017, 17(5), 318-332.
[http://dx.doi.org/10.1038/nrc.2017.8] [PMID: 28303906]
[54]
Zhang, Z.; Li, Z.; Wang, Y.; Wang, Q.; Yao, M.; Zhao, L.; Shi, J.; Guan, F.; Ma, S. PDGF-BB/SA/Dex injectable hydrogels accelerate BMSC-mediated functional full thickness skin wound repair by promoting angiogenesis. J. Mater. Chem. B Mater. Biol. Med., 2021, 9(31), 6176-6189.
[http://dx.doi.org/10.1039/D1TB00952D] [PMID: 34297017]
[55]
Lu, J.F.; Hu, Z.Q.; Yang, M.X.; Liu, W.Y.; Pan, G.F.; Ding, J.B.; Liu, J.Z.; Tang, L.; Hu, B.; Li, H.C. Downregulation of PDGF-D inhibits proliferation and invasion in breast cancer MDA-MB-231 cells. Clin. Breast Cancer, 2022, 22(2), e173-e183.
[http://dx.doi.org/10.1016/j.clbc.2021.06.002] [PMID: 34272173]
[56]
Almiron Bonnin, D.A.; Ran, C.; Havrda, M.C.; Liu, H.; Hitoshi, Y.; Zhang, Z.; Cheng, C.; Ung, M.; Israel, M.A. Insulin-mediated signaling facilitates resistance to PDGFR inhibition in proneural hPDGFB-driven gliomas. Mol. Cancer Ther., 2017, 16(4), 705-716.
[http://dx.doi.org/10.1158/1535-7163.MCT-16-0616] [PMID: 28138037]
[57]
Meng, D.; Carvajal, R.D. KIT as an oncogenic driver in melanoma: An update on clinical development. Am. J. Clin. Dermatol., 2019, 20(3), 315-323.
[http://dx.doi.org/10.1007/s40257-018-0414-1] [PMID: 30707374]
[58]
Lennartsson, J.; Rönnstrand, L. Stem cell factor receptor/c-Kit: From basic science to clinical implications. Physiol. Rev., 2012, 92(4), 1619-1649.
[http://dx.doi.org/10.1152/physrev.00046.2011] [PMID: 23073628]
[59]
Yan, W.; Zhu, Z.; Pan, F.; Huang, A.; Dai, G.H. Overexpression of c-kit(CD117), relevant with microvessel density, is an independent survival prognostic factor for patients with HBV-related hepatocellular carcinoma. OncoTargets Ther., 2018, 11, 1285-1292.
[http://dx.doi.org/10.2147/OTT.S157545] [PMID: 29563807]
[60]
Lee, E.S.; Han, E.M.; Kim, Y.S.; Shin, B.K.; Kim, C.H.; Kim, H.K.; Won, N.H.; Yeom, B.W.; Kim, I.; Leong, A.S. Occurrence of c-kit+ tumor cells in hepatitis B virus-associated hepatocellular carcinoma. Am. J. Clin. Pathol., 2005, 124(1), 31-36.
[http://dx.doi.org/10.1309/LETTWN3LUF516HR0] [PMID: 15923163]
[61]
Becker, G.; Schmitt-Graeff, A.; Ertelt, V.; Blum, H.E.; Allgaier, H.P. CD117 (c-kit) expression in human hepatocellular carcinoma. Clin. Oncol., 2007, 19(3), 204-208.
[62]
Fu, R.; Jiang, S.; Li, J.; Chen, H.; Zhang, X. Activation of the HGF/c-MET axis promotes lenvatinib resistance in hepatocellular carcinoma cells with high c-MET expression. Med. Oncol., 2020, 37(4), 24.
[http://dx.doi.org/10.1007/s12032-020-01350-4] [PMID: 32166604]
[63]
Kim, J.H.; Kim, H.S.; Kim, B.J.; Jang, H.J.; Lee, J. Prognostic value of c-Met overexpression in hepatocellular carcinoma: A meta-analysis and review. Oncotarget, 2017, 8(52), 90351-90357.
[http://dx.doi.org/10.18632/oncotarget.20087] [PMID: 29163834]
[64]
Kim, K.H.; Kim, H. Progress of antibody-based inhibitors of the HGF-cMET axis in cancer therapy. Exp. Mol. Med., 2017, 49(3), e307.
[http://dx.doi.org/10.1038/emm.2017.17] [PMID: 28336955]
[65]
Du, B.; Shim, J.S. Targeting Epithelial-Mesenchymal Transition (EMT) to overcome drug resistance in cancer. Molecules, 2016, 21(7), E965.
[http://dx.doi.org/10.3390/molecules21070965] [PMID: 27455225]
[66]
Alcedo, K.P.; Bowser, J.L.; Snider, N.T. The elegant complexity of mammalian ecto-5′-nucleotidase (CD73). Trends Cell Biol., 2021, 31(10), 829-842.
[http://dx.doi.org/10.1016/j.tcb.2021.05.008] [PMID: 34116887]
[67]
Baghbani, E.; Noorolyai, S.; Shanehbandi, D.; Mokhtarzadeh, A.; Aghebati-Maleki, L.; Shahgoli, V.K.; Brunetti, O.; Rahmani, S.; Shadbad, M.A.; Baghbanzadeh, A.; Silvestris, N.; Baradaran, B. Regulation of immune responses through CD39 and CD73 in cancer: Novel check-points. Life Sci., 2021, 282, 119826.
[http://dx.doi.org/10.1016/j.lfs.2021.119826] [PMID: 34265363]
[68]
Ma, X.L.; Shen, M.N.; Hu, B.; Wang, B.L.; Yang, W.J.; Lv, L.H.; Wang, H.; Zhou, Y.; Jin, A.L.; Sun, Y.F.; Zhang, C.Y.; Qiu, S.J.; Pan, B.S.; Zhou, J.; Fan, J.; Yang, X.R.; Guo, W. CD73 promotes hepatocellular carcinoma progression and metastasis via activating PI3K/AKT signaling by inducing Rap1-mediated membrane localization of P110β and predicts poor prognosis. J. Hematol. Oncol., 2019, 12(1), 37.
[http://dx.doi.org/10.1186/s13045-019-0724-7] [PMID: 30971294]
[69]
Gao, Z.W.; Liu, C.; Yang, L.; Chen, H.C.; Yang, L.F.; Zhang, H.Z.; Dong, K. CD73 severed as a potential prognostic marker and promote lung cancer cells migration via enhancing EMT progression. Front. Genet., 2021, 12, 728200.
[http://dx.doi.org/10.3389/fgene.2021.728200] [PMID: 34868205]
[70]
Ma, X.L.; Hu, B.; Tang, W.G.; Xie, S.H.; Ren, N.; Guo, L.; Lu, R.Q. CD73 sustained cancer-stem-cell traits by promoting SOX9 expression and stability in hepatocellular carcinoma. J. Hematol. Oncol., 2020, 13(1), 11.
[http://dx.doi.org/10.1186/s13045-020-0845-z] [PMID: 32024555]
[71]
Zheng, A.; Chevalier, N.; Calderoni, M.; Dubuis, G.; Dormond, O.; Ziros, P.G.; Sykiotis, G.P.; Widmann, C. CRISPR/Cas9 genome-wide screening identifies KEAP1 as a sorafenib, lenvatinib, and regorafenib sensitivity gene in hepatocellular carcinoma. Oncotarget, 2019, 10(66), 7058-7070.
[http://dx.doi.org/10.18632/oncotarget.27361] [PMID: 31903165]
[72]
Tsuchida, K.; Tsujita, T.; Hayashi, M.; Ojima, A.; Keleku-Lukwete, N.; Katsuoka, F.; Otsuki, A.; Kikuchi, H.; Oshima, Y.; Suzuki, M.; Yamamoto, M. Halofuginone enhances the chemo-sensitivity of cancer cells by suppressing NRF2 accumulation. Free Radic. Biol. Med., 2017, 103, 236-247.
[http://dx.doi.org/10.1016/j.freeradbiomed.2016.12.041] [PMID: 28039084]
[73]
Tao, J.; Krutsenko, Y.; Moghe, A.; Singh, S.; Poddar, M.; Bell, A.; Oertel, M.; Singhi, A.D.; Geller, D.; Chen, X.; Lujambio, A.; Liu, S.; Monga, S.P. Nuclear factor erythroid 2-related factor 2 and β-Catenin coactivation in hepatocellular cancer: Biological and therapeutic implications. Hepatology, 2021, 74(2), 741-759.
[http://dx.doi.org/10.1002/hep.31730] [PMID: 33529367]
[74]
Colozza, G.; Koo, B.K. Wnt/β-catenin signaling: Structure, assembly and endocytosis of the signalosome. Dev. Growth Differ., 2021, 63(3), 199-218.
[http://dx.doi.org/10.1111/dgd.12718] [PMID: 33619734]
[75]
Negishi, H.; Taniguchi, T.; Yanai, H. The interferon (IFN) class of cytokines and the IFN regulatory factor (IRF) transcription factor family. Cold Spring Harb. Perspect. Biol., 2018, 10(11), a028423.
[http://dx.doi.org/10.1101/cshperspect.a028423] [PMID: 28963109]
[76]
Manzella, L.; Tirrò, E.; Pennisi, M.S.; Massimino, M.; Stella, S.; Romano, C.; Vitale, S.R.; Vigneri, P. Roles of interferon regulatory factors in chronic myeloid leukemia. Curr. Cancer Drug Targets, 2016, 16(7), 594-605.
[http://dx.doi.org/10.2174/1568009616666160105105857] [PMID: 26728039]
[77]
Guo, Y.; Xu, J.; Du, Q.; Yan, Y.; Geller, D.A. IRF2 regulates cellular survival and Lenvatinib-sensitivity of hepatocellular carcinoma (HCC) through regulating β-catenin. Transl. Oncol., 2021, 14(6), 101059.
[http://dx.doi.org/10.1016/j.tranon.2021.101059] [PMID: 33735820]
[78]
Nusse, R.; Clevers, H. Wnt/β-catenin signaling, disease, and emerging therapeutic modalities. Cell, 2017, 169(6), 985-999.
[http://dx.doi.org/10.1016/j.cell.2017.05.016] [PMID: 28575679]
[79]
Cui, C.; Zhou, X.; Zhang, W.; Qu, Y.; Ke, X. Is β-catenin a druggable target for cancer therapy? Trends Biochem. Sci., 2018, 43(8), 623-634.
[http://dx.doi.org/10.1016/j.tibs.2018.06.003] [PMID: 30056837]
[80]
Wang, B.; Tian, T.; Kalland, K.H.; Ke, X.; Qu, Y. Targeting Wnt/β-catenin signaling for cancer immunotherapy. Trends Pharmacol. Sci., 2018, 39(7), 648-658.
[http://dx.doi.org/10.1016/j.tips.2018.03.008] [PMID: 29678298]
[81]
McGettrick, A.F.; O’Neill, L.A.J. The role of HIF in immunity and inflammation. Cell Metab., 2020, 32(4), 524-536.
[http://dx.doi.org/10.1016/j.cmet.2020.08.002] [PMID: 32853548]
[82]
Corrado, C.; Fontana, S. Hypoxia and HIF signaling: One axis with divergent effects. Int. J. Mol. Sci., 2020, 21(16), 5611.
[83]
Lee, S.H.; Golinska, M.; Griffiths, J.R. HIF-1-independent mechanisms regulating metabolic adaptation in hypoxic cancer cells. Cells, 2021, 10(9), 2371.
[84]
Ma, L.; Xu, A.; Kang, L.; Cong, R.; Fan, Z.; Zhu, X.; Huo, N.; Liu, W.; Xue, C.; Ji, Q.; Li, W.; Chu, Z.; Kang, X.; Wang, Y.; Sun, Z.; Han, Y.; Liu, H.; Gao, X.; Han, J.; You, H.; Zhao, C.; Xu, X. LSD1-demethylated LINC01134 confers oxaliplatin resistance through SP1-induced p62 transcription in HCC. Hepatology, 2021, 74(6), 3213-3234.
[http://dx.doi.org/10.1002/hep.32079] [PMID: 34322883]
[85]
Carbajo-Pescador, S.; Ordoñez, R.; Benet, M.; Jover, R.; García-Palomo, A.; Mauriz, J.L.; González-Gallego, J. Inhibition of VEGF expression through blockade of Hif1α and STAT3 signalling mediates the anti-angiogenic effect of melatonin in HepG2 liver cancer cells. Br. J. Cancer, 2013, 109(1), 83-91.
[http://dx.doi.org/10.1038/bjc.2013.285] [PMID: 23756865]
[86]
Rashid, M.; Zadeh, L.R.; Baradaran, B.; Molavi, O.; Ghesmati, Z.; Sabzichi, M.; Ramezani, F. Up-down regulation of HIF-1α in cancer progression. Gene, 2021, 798, 145796.
[http://dx.doi.org/10.1016/j.gene.2021.145796] [PMID: 34175393]
[87]
Liu, F.; Dong, X.; Lv, H.; Xiu, P.; Li, T.; Wang, F.; Xu, Z.; Li, J. Targeting hypoxia-inducible factor-2α enhances sorafenib antitumor activity via β-catenin/C-Myc-dependent pathways in hepatocellular carcinoma. Oncol. Lett., 2015, 10(2), 778-784.
[http://dx.doi.org/10.3892/ol.2015.3315] [PMID: 26622569]
[88]
Zhang, Q.; Bai, X.; Chen, W.; Ma, T.; Hu, Q.; Liang, C.; Xie, S.; Chen, C.; Hu, L.; Xu, S.; Liang, T. Wnt/β-catenin signaling enhances hypoxia-induced epithelial-mesenchymal transition in hepatocellular carcinoma via crosstalk with hif-1α signaling. Carcinogenesis, 2013, 34(5), 962-973.
[http://dx.doi.org/10.1093/carcin/bgt027] [PMID: 23358852]
[89]
Lee, S.H.; Kim, M.H.; Han, H.J. Arachidonic acid potentiates hypoxia-induced VEGF expression in mouse embryonic stem cells: Involvement of Notch, Wnt, and HIF-1alpha. Am. J. Physiol. Cell Physiol., 2009, 297(1), C207-C216.
[http://dx.doi.org/10.1152/ajpcell.00579.2008] [PMID: 19339510]
[90]
Xu, X.F.; Yang, X.K.; Song, Y.; Chen, B.J.; Yu, X.; Xu, T.; Chen, Z.L. Dysregulation of non-coding RNAs mediates cisplatin resistance in hepatocellular carcinoma and therapeutic strategies. Pharmacol. Res., 2022, 176, 105906.
[http://dx.doi.org/10.1016/j.phrs.2021.105906] [PMID: 34543740]
[91]
Lou, W.; Wang, W.; Chen, J.; Wang, S.; Huang, Y. ncRNAs-mediated high expression of SEMA3F correlates with poor prognosis and tumor immune infiltration of hepatocellular carcinoma. Mol. Ther. Nucleic Acids, 2021, 24, 845-855.
[http://dx.doi.org/10.1016/j.omtn.2021.03.014] [PMID: 34026328]
[92]
Xie, C.; Li, S.Y.; Fang, J.H.; Zhu, Y.; Yang, J.E. Functional long non-coding RNAs in hepatocellular carcinoma. Cancer Lett., 2021, 500, 281-291.
[http://dx.doi.org/10.1016/j.canlet.2020.10.042] [PMID: 33129957]
[93]
Wong, L.S.; Wong, C.M. Decoding the roles of long noncoding RNAs in hepatocellular carcinoma. Int. J. Mol. Sci., 2021, 22(6), 3137.
[http://dx.doi.org/10.3390/ijms22063137] [PMID: 33808647]
[94]
Shen, H.; Liu, B.; Xu, J.; Zhang, B.; Wang, Y.; Shi, L. Circular RNAs: Characteristics, biogenesis, mechanisms and functions in liver cancer. J. Hematol. Oncol., 2021, 14(1), 134.
[http://dx.doi.org/10.1186/s13045-021-01145-8]
[95]
Wang, Y.; Wang, Y.; Qin, Z. The role of non-coding RNAs in ABC transporters regulation and their clinical implications of multidrug resistance in cancer. Expert Opin. Drug Metab. Toxicol., 2021, 17(3), 291-306.
[http://dx.doi.org/10.1080/17425255.2021.1887139]
[96]
Pan, G.; Liu, Y.; Shang, L.; Zhou, F.; Yang, S. EMT-associated microRNAs and their roles in cancer stemness and drug resistance. Cancer Commun. (Lond.), 2021, 41(3), 199-217.
[http://dx.doi.org/10.1002/cac2.12138]
[97]
Khashkhashi Moghadam, S.; Bakhshinejad, B.; Khalafizadeh, A.; Mahmud Hussen, B.; Babashah, S. Non-coding RNA-associated competitive endogenous RNA regulatory networks: Novel diagnostic and therapeutic opportunities for hepatocellular carcinoma. J. Cell. Mol. Med., 2022, 26(2), 287-305.
[98]
Sorop, A.; Constantinescu, D.; Cojocaru, F.; Dinischiotu, A.; Cucu, D.; Dima, S.O. Exosomal microRNAs as biomarkers and therapeutic targets for hepatocellular carcinoma. Int. J. Mol. Sci., 2021, 22(9), 4997.
[http://dx.doi.org/10.3390/ijms22094997] [PMID: 34066780]
[99]
Song, W.; Zheng, C.; Liu, M.; Xu, Y.; Qian, Y.; Zhang, Z.; Su, H.; Li, X.; Wu, H.; Gong, P.; Li, Y.; Fan, H. TRERNA1 upregulation mediated by HBx promotes sorafenib resistance and cell proliferation in HCC via targeting NRAS by sponging miR-22-3p. Mol. Ther., 2021, 29(8), 2601-2616.
[http://dx.doi.org/10.1016/j.ymthe.2021.04.011] [PMID: 33839325]
[100]
Yu, T.; Yu, J.; Lu, L.; Zhang, Y.; Zhou, Y.; Zhou, Y. MT1JP-mediated miR-24-3p/BCL2L2 axis promotes Lenvatinib resistance in hepatocellular carcinoma cells by inhibiting apoptosis. Cell Oncol. (Dordr.), 2021, 44(4), 821-834.
[101]
Zhang, Y.; Wu, W.; Sun, Q.; Ye, L.; Zhou, D.; Wang, W. linc-ROR facilitates hepatocellular carcinoma resistance to doxorubicin by regulating TWIST1-mediated epithelial-mesenchymal transition. Mol. Med. Rep., 2021, 23(5), 340.
[http://dx.doi.org/10.3892/mmr.2021.11979]
[102]
Chen, S.; Xia, X. Long noncoding RNA NEAT1 suppresses sorafenib sensitivity of hepatocellular carcinoma cells via regulating miR-335-c-Met. J. Cell. Physiol., 2019, 234(9), 14999-15009.
[http://dx.doi.org/10.1002/jcp.27567] [PMID: 30937906]
[103]
Li, W.; Dong, X.; He, C.; Tan, G.; Li, Z.; Zhai, B.; Feng, J.; Jiang, X.; Liu, C.; Jiang, H.; Sun, X. LncRNA SNHG1 contributes to sorafenib resistance by activating the Akt pathway and is positively regulated by miR-21 in hepatocellular carcinoma cells. J. Exp. Clin. Cancer Res., 2019, 38(1), 183.
[http://dx.doi.org/10.1186/s13046-019-1177-0] [PMID: 31053148]
[104]
Ohta, K.; Hoshino, H.; Wang, J.; Ono, S.; Iida, Y.; Hata, K.; Huang, S.K.; Colquhoun, S.; Hoon, D.S. MicroRNA-93 activates c-Met/PI3K/Akt pathway activity in hepatocellular carcinoma by directly inhibiting PTEN and CDKN1A. Oncotarget, 2015, 6(5), 3211-3224.
[http://dx.doi.org/10.18632/oncotarget.3085] [PMID: 25633810]
[105]
Fornari, F.; Pollutri, D.; Patrizi, C.; La Bella, T.; Marinelli, S.; Casadei Gardini, A.; Marisi, G.; Baron Toaldo, M.; Baglioni, M.; Salvatore, V.; Callegari, E.; Baldassarre, M.; Galassi, M.; Giovannini, C.; Cescon, M.; Ravaioli, M.; Negrini, M.; Bolondi, L.; Gramantieri, L. In hepatocellular carcinoma miR-221 modulates sorafenib resistance through inhibition of caspase-3-mediated apoptosis. Clin. Cancer Res., 2017, 23(14), 3953-3965.
[http://dx.doi.org/10.1158/1078-0432.CCR-16-1464] [PMID: 28096271]
[106]
Duran, C.L.; Borriello, L.; Karagiannis, G.S.; Entenberg, D. Targeting Tie2 in the tumor microenvironment: From angiogenesis to dissemination. Cancers (Basel), 2021, 13(22), 5730.
[107]
Nakagawa, T.; Matsushima, T.; Kawano, S.; Nakazawa, Y.; Kato, Y.; Adachi, Y.; Abe, T.; Semba, T.; Yokoi, A.; Matsui, J.; Tsuruoka, A.; Funahashi, Y. Lenvatinib in combination with golvatinib overcomes hepatocyte growth factor pathway-induced resistance to vascular endothelial growth factor receptor inhibitor. Cancer Sci., 2014, 105(6), 723-730.
[http://dx.doi.org/10.1111/cas.12409] [PMID: 24689876]
[108]
Nakazawa, Y.; Kawano, S.; Matsui, J.; Funahashi, Y.; Tohyama, O.; Muto, H.; Nakagawa, T.; Matsushima, T. Multitargeting strategy using lenvatinib and golvatinib: Maximizing anti-angiogenesis activity in a preclinical cancer model. Cancer Sci., 2015, 106(2), 201-207.
[http://dx.doi.org/10.1111/cas.12581] [PMID: 25458359]
[109]
Ganesan, M.; Kanimozhi, G.; Pradhapsingh, B.; Khan, H.A.; Alhomida, A.S.; Ekhzaimy, A. Phytochemicals reverse P-glycoprotein mediated multidrug resistance via signal transduction pathways. Biomed. Pharmacother., 2021, 139, 111632.
[110]
Wei, G.; Huang, L.; Jiang, Y.; Shen, Y.; Huang, Z.; Huang, Y.; Sun, X.; Zhao, C. Lenvatinib-zinc phthalocyanine conjugates as potential agents for enhancing synergistic therapy of multidrug-resistant cancer by glutathione depletion. Eur. J. Med. Chem., 2019, 169, 53-64.
[http://dx.doi.org/10.1016/j.ejmech.2019.02.065] [PMID: 30856406]
[111]
Sun, X.; Han, L.; Seth, P.; Bian, S.; Li, L.; Csizmadia, E.; Junger, W.G.; Schmelzle, M.; Usheva, A.; Tapper, E.B.; Baffy, G.; Sukhatme, V.P.; Wu, Y.; Robson, S.C. Disordered purinergic signaling and abnormal cellular metabolism are associated with development of liver cancer in Cd39/ENTPD1 null mice. Hepatology, 2013, 57(1), 205-216.
[http://dx.doi.org/10.1002/hep.25989] [PMID: 22859060]
[112]
Nabergoj, S.; Mlinarič-Raščan, I.; Jakopin, Ž. Harnessing the untapped potential of nucleotide-binding oligomerization domain ligands for cancer immunotherapy. Med. Res. Rev., 2019, 39(5), 1447-1484.
[http://dx.doi.org/10.1002/med.21557]
[113]
Zhang, H.; Yang, S. Blockade of AMPK-mediated cAMP-PKA-CREB/ATF1 signaling synergizes with aspirin to inhibit hepatocellular carcinoma. Cancers, 2021, 13(7), 1738.
[114]
Dong, J.; Zhai, B.; Sun, W.; Hu, F.; Cheng, H.; Xu, J. Activation of phosphatidylinositol 3-kinase/AKT/snail signaling pathway contributes to epithelial-mesenchymal transition-induced multi-drug resistance to sorafenib in hepatocellular carcinoma cells. PloS One, 2017, 12(9), e0185088.
[115]
Vara, D.; Salazar, M.; Olea-Herrero, N.; Guzmán, M.; Velasco, G.; Díaz-Laviada, I. Anti-tumoral action of cannabinoids on hepatocellular carcinoma: Role of AMPK-dependent activation of autophagy. Cell Death Differ., 2011, 18(7), 1099-1111.
[http://dx.doi.org/10.1038/cdd.2011.32] [PMID: 21475304]
[116]
Guo, L.; Chen, D.; Yin, X.; Shu, Q. GSK-3β promotes cell migration and inhibits autophagy by mediating the AMPK pathway in breast cancer. Oncol. Res., 2019, 27(4), 487-494.
[http://dx.doi.org/10.3727/096504018X15323394008784] [PMID: 30037362]
[117]
Li, F.; Han, X.; Li, F.; Wang, R.; Wang, H.; Gao, Y.; Wang, X.; Fang, Z.; Zhang, W.; Yao, S.; Tong, X.; Wang, Y.; Feng, Y.; Sun, Y.; Li, Y.; Wong, K.K.; Zhai, Q.; Chen, H.; Ji, H. LKB1 inactivation elicits a redox imbalance to modulate non-small cell lung cancer plasticity and therapeutic response. Cancer Cell, 2015, 27(5), 698-711.
[http://dx.doi.org/10.1016/j.ccell.2015.04.001] [PMID: 25936644]
[118]
Peña, C.G.; Nakada, Y.; Saatcioglu, H.D.; Aloisio, G.M.; Cuevas, I.; Zhang, S.; Miller, D.S.; Lea, J.S.; Wong, K.K.; DeBerardinis, R.J.; Amelio, A.L.; Brekken, R.A.; Castrillon, D.H. LKB1 loss promotes endometrial cancer progression via CCL2-dependent macrophage recruitment. J. Clin. Invest., 2015, 125(11), 4063-4076.
[http://dx.doi.org/10.1172/JCI82152] [PMID: 26413869]
[119]
Zheng, X.; Chi, J.; Zhi, J.; Zhang, H.; Yue, D.; Zhao, J.; Li, D.; Li, Y.; Gao, M.; Guo, J. Aurora-A-mediated phosphorylation of LKB1 compromises LKB1/AMPK signaling axis to facilitate NSCLC growth and migration. Oncogene, 2018, 37(4), 502-511.
[http://dx.doi.org/10.1038/onc.2017.354] [PMID: 28967900]
[120]
Faubert, B.; Boily, G.; Izreig, S.; Griss, T.; Samborska, B.; Dong, Z.; Dupuy, F.; Chambers, C.; Fuerth, B.J.; Viollet, B.; Mamer, O.A.; Avizonis, D.; DeBerardinis, R.J.; Siegel, P.M.; Jones, R.G. AMPK is a negative regulator of the Warburg effect and suppresses tumor growth in vivo. Cell Metab., 2013, 17(1), 113-124.
[http://dx.doi.org/10.1016/j.cmet.2012.12.001] [PMID: 23274086]
[121]
Ma, X.; Qiu, Y.; Sun, Y.; Zhu, L.; Zhao, Y.; Li, T.; Lin, Y.; Ma, D.; Qin, Z.; Sun, C.; Han, L. NOD2 inhibits tumorigenesis and increases chemosensitivity of hepatocellular carcinoma by targeting AMPK pathway. Cell Death Dis., 2020, 11(3), 174.
[http://dx.doi.org/10.1038/s41419-020-2368-5] [PMID: 32144252]
[122]
Zhu, J.; Li, R.; Tiselius, E.; Roudi, R.; Teghararian, O.; Suo, C.; Song, H. Immunotherapy (excluding checkpoint inhibitors) for stage I to III non-small cell lung cancer treated with surgery or radiotherapy with curative intent. Cochrane Database Syst. Rev., 2017, 12(12), CD011300.
[http://dx.doi.org/10.1002/14651858.CD011300.pub2] [PMID: 29247502]
[123]
Roudi, R; D'Angelo, A; Sirico, M; Sobhani, N Immunotherapeutic treatments in hepatocellular carcinoma; achievements, challenges and future prospects. Int. Immunopharmacol., 2021, 101(Pt A), 108322.
[124]
Inno, A.; Roviello, G.; Ghidini, A.; Luciani, A.; Catalano, M.; Gori, S.; Petrelli, F. Rechallenge of immune checkpoint inhibitors: A systematic review and meta-analysis. Crit. Rev. Oncol. Hematol., 2021, 165, 103434.
[http://dx.doi.org/10.1016/j.critrevonc.2021.103434] [PMID: 34343657]
[125]
Wang, Y.; Sun, Q.; Mu, N.; Sun, X.; Wang, Y.; Fan, S.; Su, L.; Liu, X. The deubiquitinase USP22 regulates PD-L1 degradation in human cancer cells. Cell Commun. Signal., 2020, 18(1), 112.
[http://dx.doi.org/10.1186/s12964-020-00612-y] [PMID: 32665011]
[126]
Tan, Y.; Xu, Q.; Wu, Z.; Zhang, W.; Li, B.; Zhang, B.; Xu, X.; Zhang, B.; Yan, K.; Song, J.; Lv, T.; Yang, J.; Jiang, L.; Shi, Y.; Yang, J.; Yan, L. Overexpression of PD-L1 is an independent predictor for recurrence in HCC patients who receive sorafenib treatment after surgical resection. Front. Oncol., 2022, 11, 783335.
[http://dx.doi.org/10.3389/fonc.2021.783335] [PMID: 35117990]
[127]
Liang, Y.; Li, L.; Chen, Y.; Xiao, J.; Wei, D. PD-1/PD-L1 immune checkpoints: Tumor vs atherosclerotic progression. Clin. Chim. Acta, 2021, 519, 70-75.
[128]
Dai, X.; Xue, J.; Hu, J.; Yang, S.L.; Chen, G.G.; Lai, P.B.S.; Yu, C.; Zeng, C.; Fang, X.; Pan, X.; Zhang, T. Positive expression of programmed death ligand 1 in peritumoral liver tissue is associated with poor survival after curative resection of hepatocellular carcinoma. Transl. Oncol., 2017, 10(4), 511-517.
[http://dx.doi.org/10.1016/j.tranon.2017.03.009] [PMID: 28558264]
[129]
Dong, Y.; Wong, J.S.L.; Sugimura, R. Recent advances and future prospects in immune checkpoint (ICI)-based combination therapy for advanced HCC. Cancers (Basel), 2021, 13(8), 1949.
[130]
Kudo, M.; Lim, H.Y.; Cheng, A.L.; Chao, Y.; Yau, T.; Ogasawara, S.; Kurosaki, M.; Morimoto, N.; Ohkawa, K.; Yamashita, T.; Lee, K.H.; Chen, E.; Siegel, A.B.; Ryoo, B.Y. Pembrolizumab as second-line therapy for advanced hepatocellular carcinoma: A subgroup analysis of asian patients in the phase 3 KEYNOTE-240 trial. Liver Cancer, 2021, 10(3), 275-284.
[http://dx.doi.org/10.1159/000515553] [PMID: 34239813]
[131]
Zhu, A.X.; Finn, R.S.; Edeline, J.; Cattan, S.; Ogasawara, S.; Palmer, D.; Verslype, C.; Zagonel, V.; Fartoux, L.; Vogel, A.; Sarker, D.; Verset, G.; Chan, S.L.; Knox, J.; Daniele, B.; Webber, A.L.; Ebbinghaus, S.W.; Ma, J.; Siegel, A.B.; Cheng, A.L.; Kudo, M.; Alistar, A.; Asselah, J.; Blanc, J-F.; Borbath, I.; Cannon, T.; Chung, K.; Cohn, A.; Cosgrove, D.P.; Damjanov, N.; Gupta, M.; Karino, Y.; Karwal, M.; Kaubisch, A.; Kelley, R.; Van Laethem, JL.; Larson, T.; Lee, J.; Li, D.; Manhas, A.; Manji, G.A.; Numata, K.; Parsons, B.; Paulson, A.S.; Pinto, C.; Ramirez, R.; Ratnam, S.; Rizell, M.; Rosmorduc, O.; Sada, Y.; Sasaki, Y.; Stal, P.I.; Strasser, S.; Trojan, J.; Vaccaro, G.; Van Vlierberghe, H.; Weiss, A.; Weiss, K-H.; Yamashita, T. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): A non-randomised, open-label phase 2 trial. Lancet Oncol., 2018, 19(7), 940-952.
[http://dx.doi.org/10.1016/S1470-2045(18)30351-6] [PMID: 29875066]
[132]
Finn, R.S.; Ikeda, M.; Zhu, A.X.; Sung, M.W.; Baron, A.D.; Kudo, M.; Okusaka, T.; Kobayashi, M.; Kumada, H.; Kaneko, S.; Pracht, M.; Mamontov, K.; Meyer, T.; Kubota, T.; Dutcus, C.E.; Saito, K.; Siegel, A.B.; Dubrovsky, L.; Mody, K.; Llovet, J.M. Phase Ib study of lenvatinib plus pembrolizumab in patients with unresectable hepatocellular carcinoma. J. Clin. Oncol., 2020, 38(26), 2960-2970.
[http://dx.doi.org/10.1200/JCO.20.00808] [PMID: 32716739]
[133]
Jacob, A.; Shook, J.; Hutson, T. The implementation of lenvatinib/everolimus or lenvatinib/pembrolizumab combinations in the treatment of metastatic renal cell carcinoma. Expert Rev. Anticancer Ther., 2021, 21(4), 365-372.
[http://dx.doi.org/10.1080/14737140.2021.1868994] [PMID: 33393393]

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