Chinese Medical Sciences Journal ›› 2021, Vol. 36 ›› Issue (1): 57-65.doi: 10.24920/003737
收稿日期:
2020-03-06
接受日期:
2020-05-11
出版日期:
2021-03-31
通讯作者:
阳学风
E-mail:yxf9988@126.com
Received:
2020-03-06
Accepted:
2020-05-11
Published:
2021-03-31
Contact:
Xuefeng Yang
E-mail:yxf9988@126.com
摘要:
肝细胞癌(Hepatocellular carcinoma,HCC)是常见的恶性肿瘤之一,治疗手段有限。随着肝癌发生发展过程中关键基因和信号通路认识的深入,一些高选择性、低毒性的靶向药物不断问世,为晚期肝癌的治疗带来了多种选择。本文综述了肝细胞癌靶向治疗的代表性药物和潜在靶点的研究进展。
Qiong Chen,Xuefeng Yang. Research Progress in Targeted Therapy of Hepatocellular Carcinoma[J].Chinese Medical Sciences Journal, 2021, 36(1): 57-65.
1. |
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. doi: 10.1038/s41575-019-0186-y.
doi: 10.1038/s41575-019-0186-y pmid: 31439937 |
2. |
Wang H, Lu Z, Zhao X. Tumorigenesis, diagnosis, and therapeutic potential of exosomes in liver cancer. J Hematol Oncol 2019; 12(1):133. doi: 10.1186/s13045-019-0806-6.
doi: 10.1186/s13045-019-0806-6 pmid: 31815633 |
3. |
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. doi: 10.1038/s41571-018-0073-4.
doi: 10.1038/s41571-018-0073-4 pmid: 30061739 |
4. |
Couri T, Pillai A. Goals and targets for personalized therapy for HCC. Hepatol Int 2019; 13(2):125-37. doi: 10.1007/s12072-018-9919-1.
doi: 10.1007/s12072-018-9919-1 pmid: 30600478 |
5. |
Pinter M, Peck-Radosavljevic M. Review article: systemic treatment of hepatocellular carcinoma. Aliment Pharmacol Ther 2018; 48(6):598-609. doi: 10.1111/apt.14913.
doi: 10.1111/apt.14913 pmid: 30039640 |
6. |
Li M, Su Y, Zhang F, et al. A dual-targeting reconstituted high density lipoprotein leveraging the synergy of sorafenib and antimiRNA21 for enhanced hepatocellular carcinoma therapy. Acta Biomater 2018; 75:413-26. doi: 10.1016/j.actbio.2018.05.049.
doi: 10.1016/j.actbio.2018.05.049 pmid: 29859368 |
7. |
Matsuki M, Hoshi T, Yamamoto Y, et al. Lenvatinib inhibits angiogenesis and tumor fibroblast growth factor signaling pathways in human hepatocellular carcinoma models. Cancer Med 2018; 7(6):2641-53. doi: 10.1002/cam4.1517.
pmid: 29733511 |
8. |
Hoshi T, Watanabe MS, Watanabe H, et al. Lenvatinib induces death of human hepatocellular carcinoma cells harboring an activated FGF signaling pathway through inhibition of FGFR-MAPK cascades. Biochem Biophys Res Commun 2019; 513(1):1-7. doi: 10.1016/j.bbrc.2019.02.015.
doi: 10.1016/j.bbrc.2019.02.015 pmid: 30944079 |
9. |
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 non-inferiority trial. Lancet 2018; 391(10126):1163-73. doi: 10.1016/S0140-6736(18)30207-1.
pmid: 29433850 |
10. |
Kobayashi M, Kudo M, Izumi N, et al. Cost-effectiveness analysis of lenvatinib treatment for patients with unresectable hepatocellular carcinoma (uHCC) compared with sorafenib in Japan. J Gastroenterol 2019; 54(6):558-70. doi: 10.1007/s00535-019-01554-0.
doi: 10.1007/s00535-019-01554-0 pmid: 30788569 |
11. |
Bruix J, Qin S, Merle P, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017; 389(10064):56-66. doi: 10.1016/S0140-6736(16)32453-9.
doi: 10.1016/S0140-6736(16)32453-9 pmid: 27932229 |
12. |
Ogasawara S, Ooka Y, Itokawa N, et al. Sequential therapy with sorafenib and regorafenib for advanced hepatocellular carcinoma: a multicenter retrospective study in Japan. Invest New Drugs 2020; 38(1):172-80. doi: 10.1007/s10637-019-00801-8.
doi: 10.1007/s10637-019-00801-8 pmid: 31172442 |
13. |
Yoo C, Park JW, Kim YJ, et al. Multicenter retrospective analysis of the safety and efficacy of regorafenib after progression on sorafenib in Korean patients with hepatocellular carcinoma. Invest New Drugs 2019; 37(3):567-72. doi: 10.1007/s10637-018-0707-5.
doi: 10.1007/s10637-018-0707-5 pmid: 30523474 |
14. |
Ogasawara S, Chiba T, Ooka Y, et al. Characteristics of patients with sorafenib-treated advanced hepatocellular carcinoma eligible for second-line treatment. Invest New Drugs 2018; 36(2):332-9. doi: 10.1007/s10637-017-0507-3.
doi: 10.1007/s10637-017-0507-3 pmid: 28891038 |
15. |
Finn RS, Merle P, Granito A, et al. Outcomes of sequential treatment with sorafenib followed by regorafenib for HCC: Additional analyses from the phase III RESORCE trial. J Hepatol 2018; 69(2):353-8. doi: 10.1016/j.jhep.2018.04.010.
doi: 10.1016/j.jhep.2018.04.010 pmid: 29704513 |
16. |
Yang C, Qin S. Apatinib targets both tumor and endothelial cells in hepatocellular carcinoma. Cancer Med 2018; 7(9):4570-83. doi: 10.1002/cam4.1664.
doi: 10.1002/cam4.1664 pmid: 30109780 |
17. |
Zhang H, Cao Y, Chen Y, et al. Apatinib promotes apoptosis of the SMMC-7721 hepatocellular carcinoma cell line via the PI3K/Akt pathway. Oncol Lett 2018; 15(4):5739-43. doi: 10.3892/ol.2018.8031.
doi: 10.3892/ol.2018.8031 pmid: 29552208 |
18. | Yu WC, Zhang KZ, Chen SG, et al. Efficacy and Safety of apatinib in patients with intermediate/advanced hepatocellular carcinoma: A prospective observation study. Medicine (Baltimore) 2018; 97(3):e9704. doi: 10.1097/MD.0000000000009704. |
19. |
Xue JM, Astère M, Zhong MX, et al. Efficacy and safety of apatinib treatment for gastric cancer, hepatocellular carcinoma and non-small cell lung cancer: a meta-analysis. Onco Targets Ther 2018; 11:6119-28. doi: 10.2147/OTT.S172717.
doi: 10.2147/OTT.S172717 pmid: 30288047 |
20. | Wang Y, Gou Q, Xu R, et al. Efficacy and safety of sorafenib versus apatinib in the treatment of intermediate and advanced hepatocellular carcinoma: a comparative retrospective study. Onco Targets Ther 2018; 11:3407-13. doi: 10.2147/OTT.S161023. |
21. |
Wang Y, Tang Z. A novel long-sustaining system of apatinib for long-term inhibition of the proliferation of hepatocellular carcinoma cells. Onco Targets Ther 2018; 11:8529-41. doi: 10.2147/OTT.S188209.
doi: 10.2147/OTT.S188209 pmid: 30555243 |
22. |
Liu Z, Wang C, Wu G, et al. MRI analysis of hydrogel-loaded apatinib for local therapy of hepatocellular carcinoma model in nude mice. Biochem Biophys Res Commun 2019; 509(2):529-34. doi: 10.1016/j.bbrc.2018.12.120.
doi: 10.1016/j.bbrc.2018.12.120 pmid: 30598262 |
23. |
Zhu Y, Feng B, Mei L, et al. Clinical efficacy of TACE combined with Apatinib in the treatment of advanced hepatocellular carcinoma. J BUON 2019; 24(2):608-14. doi: 10.1109/5.771073.
pmid: 31128013 |
24. |
Liu C, Xing W, Si T, et al. Efficacy and safety of apatinib combined with transarterial chemoembolization for hepatocellular carcinoma with portal venous tumor thrombus: a retrospective study. Oncotarget 2017; 8(59):100734-45. doi: 10.18632/oncotarget.20140.
pmid: 29246017 |
25. |
Lu W, Jin XL, Yang C, et al. Comparison of efficacy between TACE combined with apatinib and TACE alone in the treatment of intermediate and advanced hepatocellular carcinoma: A single-center randomized controlled trial. Cancer Biol Ther 2017; 18(6):433-8. doi: 10.1080/15384047.2017.1323589.
doi: 10.1080/15384047.2017.1323589 pmid: 28548587 |
26. |
Zhu AX, Finn RS, Mulcahy M, et al. A phase II and biomarker study of ramucirumab, a human monoclonal antibody targeting the VEGF receptor-2, as first-line monotherapy in patients with advanced hepatocellular cancer. Clin Cancer Res 2013; 19(23):6614-23. doi: 10.1158/1078-0432.CCR-13-1442.
doi: 10.1158/1078-0432.CCR-13-1442 pmid: 24088738 |
27. |
Chau I, Peck-Radosavljevic M, Borg C, et al. Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib: Patient-focused outcome results from the randomised phase III REACH study. Eur J Cancer 2017; 81:17-25. doi: 10.1016/j.ejca.2017.05.001.
doi: 10.1016/j.ejca.2017.05.001 pmid: 28591675 |
28. |
Zhu AX, Kang YK, Yen CJ, et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2019; 20(2):282-96. doi: 10.1016/S1470-2045(18)30937-9.
doi: 10.1016/S1470-2045(18)30937-9 pmid: 30665869 |
29. |
Siegel AB, Cohen EI, Ocean A, et al. Phase II trial evaluating the clinical and biologic effects of bevacizumab in unresectable hepatocellular carcinoma. J Clin Oncol 2008; 26(18):2992-8. doi: 10.1200/JCO.2007.15.9947.
doi: 10.1200/JCO.2007.15.9947 pmid: 18565886 |
30. |
Hubbard JM, Mahoney MR, Loui WS, et al. Phase I/II Randomized Trial of Sorafenib and Bevacizumab as First-Line Therapy in Patients with Locally Advanced or Metastatic Hepatocellular Carcinoma: North Central Cancer Treatment Group Trial N0745 (Alliance). Target Oncol 2017; 12(2):201-9. doi: 10.1007/s11523-016-0467-0.
doi: 10.1007/s11523-016-0467-0 pmid: 27943153 |
31. |
Thomas MB, Garrett-Mayer E, Anis M, et al. A randomized phase II open-label multi-institution study of the combination of bevacizumab and erlotinib compared to sorafenib in the first-line treatment of patients with advanced hepatocellular carcinoma. Oncology 2018; 94(6):329-39. doi: 10.1159/000485384.
doi: 10.1159/000485384 pmid: 29719302 |
32. |
Cheng AL, Kang YK, Lin DY, et al. Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase III trial. J Clin Oncol 2013; 31(32):4067-75. doi: 10.1200/JCO.2012.45.8372.
doi: 10.1200/JCO.2012.45.8372 pmid: 24081937 |
33. |
Pokuri VK, Tomaszewski GM, Ait-Oudhia S, et al. Efficacy, Safety, and Potential Biomarkers of Sunitinib and Transarterial Chemoembolization (TACE) Combination in Advanced Hepatocellular Carcinoma (HCC): Phase II Trial. Am J Clin Oncol 2018; 41(4):332-8. doi: 10.1097/COC.0000000000000286.
doi: 10.1097/COC.0000000000000286 pmid: 27014931 |
34. |
Johnson PJ, Qin S, Park JW, et al. 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):3517-24. doi: 10.1200/JCO.2012.48.4410.
doi: 10.1200/JCO.2012.48.4410 pmid: 23980084 |
35. |
Llovet JM, Decaens T, Raoul JL, et al. Brivanib in patients with advanced hepatocellular carcinoma who were intolerant to sorafenib or for whom sorafenib failed: results from the randomized phase III BRISK-PS study. J Clin Oncol 2013; 31(28):3509-16. doi: 10.1200/JCO.2012.47.3009.
doi: 10.1200/JCO.2012.47.3009 pmid: 23980090 |
36. |
Qu Z, Jiang C, Wu J, et al. Lenalidomide induces apoptosis and inhibits angiogenesis via caspase-3 and VEGF in hepatocellular carcinoma cells. Mol Med Rep 2016; 14(5):4781-6. doi: 10.3892/mmr.2016.5797. Epub 2016 Oct 5.
doi: 10.3892/mmr.2016.5797 pmid: 27748917 |
37. |
Maria de Souza C, Fonseca de Carvalho L, da Silva Vieira T, et al. Thalidomide attenuates mammary cancer associated-inflammation, angiogenesis and tumor growth in mice. Biomed Pharmacother 2012; 66(7):491-8. doi: 10.1016/j.biopha.2012.04.005.
doi: 10.1016/j.biopha.2012.04.005 pmid: 22705333 |
38. |
Shao YY, Chen BB, Ou DL, et al. Lenalidomide as second-line therapy for advanced hepatocellular carcinoma: exploration of biomarkers for treatment efficacy. Aliment Pharmacol Ther 2017; 46(8):722-30. doi: 10.1111/apt.14270.
doi: 10.1111/apt.14270 pmid: 28815645 |
39. |
Ye Q, Qin S, Liu Y, et al. Inhibitory effect of endostar on specific angiogenesis induced by human hepatocellular carcinoma. Gastroenterol Res Pract 2015; 2015:957574. doi: 10.1155/2015/957574.
doi: 10.1155/2015/957574 pmid: 25983751 |
40. |
Zhu AX, Ancukiewicz M, Supko JG, et al. Efficacy, safety, pharmacokinetics, and biomarkers of cediranib monotherapy in advanced hepatocellular carcinoma: a phase II study. Clin Cancer Res 2013; 19(6):1557-66. doi: 10.1158/1078-0432.CCR-12-3041.
doi: 10.1158/1078-0432.CCR-12-3041 pmid: 23362324 |
41. |
Kang YK, Yau T, Park JW, et al. Randomized phase II study of axitinib versus placebo plus best supportive care in second-line treatment of advanced hepatocellular carcinoma. Ann Oncol 2015; 26(12):2457-63. doi: 10.1093/annonc/mdv388.
doi: 10.1093/annonc/mdv388 pmid: 26386123 |
42. |
Cainap C, Qin S, Huang WT, et al. Linifanib versus Sorafenib in patients with advanced hepatocellular carcinoma: results of a randomized phase III trial. J Clin Oncol 2015; 33(2):172-9. doi: 10.1200/JCO.2013.54.3298.
doi: 10.1200/JCO.2013.54.3298 pmid: 25488963 |
43. |
Chen YJ, Chi CW, Su WC, et al. Lapatinib induces autophagic cell death and inhibits growth of human hepatocellular carcinoma. Oncotarget 2014; 5(13):4845-54. doi: 10.18632/oncotarget.2045.
doi: 10.18632/oncotarget.2045 pmid: 24947784 |
44. |
Chen JY, Huang WC, Wei CT, et al. The C-terminus of hepatitis B virus-encoded X protein is required for lapatinib sensitivity in hepatocellular carcinoma cells. Anticancer Res 2019; 39(2):721-6. doi: 10.21873/anticanres.13168.
doi: 10.21873/anticanres.13168 pmid: 30711950 |
45. |
Huether A, Höpfner M, Baradari V, et al. EGFR blockade by cetuximab alone or as combination therapy for growth control of hepatocellular cancer. Biochem Pharmacol 2005; 70(11):1568-78. doi: 10.1016/j.bcp.2005.09.007.
doi: 10.1016/j.bcp.2005.09.007 pmid: 16226226 |
46. |
Geng J, Li X, Lang X, et al. Combination of cetuximab and rapamycin enhances the therapeutic efficacy in hepatocellular carcinoma. Technol Cancer Res Treat 2014; 13(4):377-85. doi: 10.7785/tcrt.2012.500389.
doi: 10.7785/tcrt.2012.500389 pmid: 24325131 |
47. |
Zhang J, Zong Y, Xu GZ, et al. Erlotinib for advanced hepatocellular carcinoma. A systematic review of phase II/III clinical trials. Saudi Med J 2016; 37(11):1184-90. doi: 10.15537/smj.2016.11.16267.
doi: 10.15537/smj.2016.11.16267 pmid: 27761555 |
48. |
Zhu AX, Rosmorduc O, Evans TR, et al. SEARCH: a phase III, randomized, double-blind, placebo-controlled trial of sorafenib plus erlotinib in patients with advanced hepatocellular carcinoma. J Clin Oncol 2015; 33(6):559-66. doi: 10.1200/JCO.2013.53.7746.
doi: 10.1200/JCO.2013.53.7746 pmid: 25547503 |
49. |
He L, Deng H, Lei J, et al. Efficacy of bevacizumab combined with erlotinib for advanced hepatocellular carcinoma: a single-arm meta-analysis based on prospective studies. BMC Cancer 2019; 19(1):276. doi: 10.1186/s12885-019-5487-6.
doi: 10.1186/s12885-019-5487-6 pmid: 30922256 |
50. |
Yanik EL, Chinnakotla S, Gustafson SK, et al. Effects of maintenance immunosuppression with sirolimus after liver transplant for hepatocellular carcinoma. Liver Transpl 2016; 22(5):627-34. doi: 10.1002/lt.24395.
doi: 10.1002/lt.24395 pmid: 26784951 |
51. |
Geissler EK, Schnitzbauer AA, Zülke C, et al. Sirolimus use in liver transplant recipients with hepatocellular carcinoma: a randomized, multicenter, open-label phase 3 trial. Transplantation 2016; 100(1):116-25. doi: 10.1097/TP.0000000000000965.
doi: 10.1097/TP.0000000000000965 pmid: 26555945 |
52. |
Zhu AX, Kudo M, Assenat E, et al. Effect of everolimus on survival in advanced hepatocellular carcinoma after failure of sorafenib: the EVOLVE-1 randomized clinical trial. JAMA 2014; 312(1):57-67. doi: 10.1001/jama.2014.7189.
doi: 10.1001/jama.2014.7189 pmid: 25058218 |
53. |
Koeberle D, Dufour JF, Demeter G, et al. Sorafenib with or without everolimus in patients with advanced hepatocellular carcinoma (HCC): a randomized multicenter, multinational phase II trial (SAKK 77/08 and SASL 29). Ann Oncol 2016; 27(5):856-61. doi: 10.1093/annonc/mdw054.
doi: 10.1093/annonc/mdw054 pmid: 26884590 |
54. |
TCC Y, Lencioni R, Sukeepaisarnjaroen W, et al. A phase Ⅰ/Ⅱ multicenter study of single-agent foretinib as first-line therapy in patients with advanced hepatocellular carcinoma. Clin Cancer Res 2017; 23(10):2405-13. doi: 10.1158/1078-0432.CCR-16-1789.
doi: 10.1158/1078-0432.CCR-16-1789 pmid: 27821605 |
55. |
Abou-Alfa GK, Meyer T, Cheng AL, et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med 2018; 379(1):54-63. doi: 10.1056/NEJMoa1717002.
doi: 10.1056/NEJMoa1717002 pmid: 29972759 |
56. |
Soto-Perez-de-Celis E, Aguiar PN, Cordón ML, et al. Cost-effectiveness of cabozantinib in the second-line treatment of advanced hepatocellular carcinoma. J Natl Compr Canc Netw 2019; 17(6):669-75. doi: 10.6004/jnccn.2018.7275.
doi: 10.6004/jnccn.2018.7275 pmid: 31200357 |
57. |
Ringelhan M, Pfister D, O’Connor T, et al. The immunology of hepatocellular carcinoma. Nat Immunol 2018; 19(3):222-32. doi: 10.1038/s41590-018-0044-z.
doi: 10.1038/s41590-018-0044-z pmid: 29379119 |
58. |
Facciorusso A, Licinio R, Carr BI, et al. MEK 1/2 inhibitors in the treatment of hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol 2015; 9(7):993-1003. doi: 10.1586/17474124.2015.1040763.
doi: 10.1586/17474124.2015.1040763 pmid: 25915713 |
59. |
Tai WM, Yong WP, Lim C, et al. A phase Ib study of selumetinib (AZD6244, ARRY-142886) in combination with sorafenib in advanced hepatocellular carcinoma (HCC). Ann Oncol 2018; 29(2):526. doi: 10.1093/annonc/mdx060.
doi: 10.1093/annonc/mdx060 pmid: 28368515 |
60. |
Lim HY, Heo J, Choi HJ, et al. A phase II study of the efficacy and safety of the combination therapy of the MEK inhibitor refametinib (BAY 86-9766) plus sorafenib for Asian patients with unresectable hepatocellular carcinoma. Clin Cancer Res 2014; 20(23):5976-85. doi: 10.1158/1078-0432.CCR-13-3445.
doi: 10.1158/1078-0432.CCR-13-3445 pmid: 25294897 |
61. |
Lim HY, Merle P, Weiss KH, et al. Phase II studies with refametinib or refametinib plus sorafenib in patients with RAS-mutated hepatocellular carcinoma. Clin Cancer Res 2018; 24(19):4650-61. doi: 10.1158/1078-0432.CCR-17-3588.
doi: 10.1158/1078-0432.CCR-17-3588 pmid: 29950351 |
62. |
Abou-Alfa GK, Capanu M, O’Reilly EM, et al. A phase II study of cixutumumab (IMC-A12, NSC742460) in advanced hepatocellular carcinoma. J Hepatol 2014; 60(2):319-24. doi: 10.1016/j.jhep.2013.09.008.
doi: 10.1016/j.jhep.2013.09.008 pmid: 24045151 |
63. |
El-Khoueiry AB, O’Donnell R, Semrad TJ, et al. A phase I trial of escalating doses of cixutumumab (IMC-A12) and sorafenib in the treatment of advanced hepatocellular carcinoma. Cancer Chemother Pharmacol 2018; 81(5):957-63. doi: 10.1007/s00280-018-3553-4.
doi: 10.1007/s00280-018-3553-4 pmid: 29520435 |
64. |
Scott LJ. Larotrectinib: First Global Approval. Drugs 2019; 79(2):201-6. doi: 10.1007/s40265-018-1044-x.
doi: 10.1007/s40265-018-1044-x pmid: 30635837 |
65. |
Liu D, Offin M, Harnicar S, et al. Entrectinib: an orally available, selective tyrosine kinase inhibitor for the treatment of NTRK, ROS1, and ALK fusion-positive solid tumors. Ther Clin Risk Manag 2018; 14:1247-52. doi: 10.2147/TCRM.S147381.
doi: 10.2147/TCRM.S147381 pmid: 30050303 |
66. |
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. doi: 10.1016/S1470-2045(19)30691-6.
doi: 10.1016/S1470-2045(19)30691-6 pmid: 31838007 |
67. |
Tomás-Loba A, Manieri E, González-Terán B, et al. p38γ is essential for cell cycle progression and liver tumorigenesis. Nature 2019; 568(7753):557-60. doi: 10.1038/s41586-019-1112-8.
doi: 10.1038/s41586-019-1112-8 pmid: 30971822 |
68. |
Chen DT, Pan JH, Chen YH, et al. The mu-opioid receptor is a molecular marker for poor prognosis in hepatocellular carcinoma and represents a potential therapeutic target. Br J Anaesth 2019; 122(6):e157-e167. doi: 10.1016/j.bja.2018.09.030.
doi: 10.1016/j.bja.2018.09.030 pmid: 30915986 |
69. |
Chan KK, Leung CO, Wong CC, et al. Secretory Stanniocalcin 1 promotes metastasis of hepatocellular carcinoma through activation of JNK signaling pathway. Cancer Lett 2017; 403:330-8. doi: 10.1016/j.canlet.2017.06.034.
doi: 10.1016/j.canlet.2017.06.034 pmid: 28688970 |
70. | Moon H, Cho K, Shin S, et al. High risk of hepatocellular carcinoma development in fibrotic liver: role of the hippo-yap/taz signaling pathway. Int J Mol Sci 2019; 20(3):581. doi: 10.3390/ijms20030581. |
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