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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Issue 7
Jul.  2018
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Article Contents

Advances in molecular targeted therapy for hepatocellular carcinoma

DOI: 10.3969/j.issn.1001-5256.2018.07.005
  • Received Date: 2018-04-08
  • Published Date: 2018-07-20
  • At present, the main treatment methods for hepatocellular carcinoma ( HCC) include surgery, chemotherapy, and radiotherapy.With the development of molecular biological techniques, the field of molecular targeted therapy is developing rapidly. The design of targeted drugs based on some specific sites in the signaling pathways involved in the development and progression of HCC has become a new research hotspot. This article elaborates on the pathways involved in the development and progression of HCC and targeted drugs for treatment.

     

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  • [1]TORRE LA, BRAY F, SIEGEL RL, et al.Global cancer statistics, 2012[J].CA Cancer J Clin, 2015, 65 (2) :87-108.
    [2]CHEN WQ, ZHENG RS, BAADE PD, et al.Cancer statistics in China, 2015[J].CA Cancer J Clin, 2016, 66 (2) :115-1132.
    [3]de MARTEL C, FERLAY J, FRANCESCHI S, et al.Global burden of cancers attributable to infections in 2008:A review and synthetic analysis[J].Lancet Oncol, 2012, 13 (6) :607-615.
    [4] EL-SERAG HB.Hepatocellular carcinoma[J].N Engl J Med, 2011, 365 (12) :1118-1127.
    [5]MITTAL S, EL-SERAG HB.Epidemiology of hepatocellular carcinoma:Consider the population[J].J Clin Gastroenterol, 2013, 47 (Suppl) :s2-s6.
    [6]LINHART KB, GLASSEN K, PECCERELLA T, et al.The generation of carcinogenic etheno-DNA adducts in the liver of patients with nonalcoholic fatty liver disease[J].Hepatobiliary Surg Nutr, 2015, 4 (2) :117-123.
    [7]GHOURI YA, MIAN I, ROWE JH.Review of hepatocellular carcinoma:Epidemiology, etiology, and carcinogenesis[J].J Carcinog, 2017, 16 (1) :1.
    [8]WANG J, YANG T, CHEN H, et al.Oncogene RPA1 promotes proliferation of hepatocellular carcinoma via CDK4/Cyclin-D pathway[J].Biochem Biophys Res Commun, 2018, 498 (3) :424-430.
    [9]SHENG XR, XING SG, WANG RD, et al.Low levels of tumor suppressor candidate 3 predict poor prognosis of patients with hepatocellular carcinoma[J].Onco Targets Ther, 2018, 11:909-917.
    [10]KUDO M.Signaling pathway and molecular-targeted therapy for hepatocellular carcinoma[J].Dig Dis, 2011, 29 (3) :289-302.
    [11]XIA H, DAI X, YU H, et al.EGFR-PI3K-PDK1 pathway regulates YAP signaling in hepatocellular carcinoma:The mechanism and its implications in targeted therapy[J].Cell Death Dis, 2018, 9 (3) :269.
    [12]VILLANUEVA A, NEWELL P, CHIANG DY, et al.Genomics and signaling pathways in hepatocellular carcinoma[J].Semin Liver Dis, 2007, 27 (1) :55-76.
    [13]DELLA CORTE CM, VISCARDI G, PAPACCIO F, et al.Implication of the hedgehog pathway in hepatocellular carcinoma[J].World J Gastroenterol, 2017, 23 (24) :4330-4340.
    [14]XIONG S, WANG R, CHEN Q, et al.Cancer-associated fibroblasts promote stem cell-like properties of hepatocellular carcinoma cells through IL-6/STAT3/Notch signaling[J].Am J Cancer Res, 2018, 8 (2) :302-316.
    [15] LIU L, CAO Y, CHEN C, et al.Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumorcell apoptosis in hepatocellular carcinoma model PLC/PRF/5[J].Cancer Res, 2006, 66 (24) :11851-11858.
    [16] LLOVET JM, RICCI S, MAZZAFERRO V, et al.Sorafenib in advanced hepatocellular carcinoma[J].N Engl J Med, 2008, 359 (4) :378-390.
    [17]CHENG AL, KANG YK, EHEN Z, et al.Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma:A phase III randomised, double-blind, placebo-controlled trial[J].Lancet Oncol, 2009, 10 (1) :25-34.
    [18]YE SL, YANG J, BIE P, et al.Safety assessment of sorafenib in Chinese patients with unresectable hepatocellular carcinoma:Subgroup analysis of the GIDEON study[J].BMC Cancer, 2018, 18 (1) :247.
    [19]WADA Y, TAKAMI Y, MATSUSHIMA H, et al.The safety and efficacy of combination therapy of sorafenib and radiotherapy for advanced hepatocellular carcinoma:A retrospective study[J].Intern Med, 2017, 57 (10) :1345-1353.
    [20]KODAMA K, KAWAOKA T, AIKATA H, et al.Comparison of outcome of hepatic arterial infusion chemotherapy combined with radiotherapy and sorafenib for advanced hepatocellular carcinoma patients with major portal vein tumor thrombosis[J].Oncology, 2018, 94 (4) :215-222.
    [21]CHAO Y, CHUNG YH, HAN G, et al.The combination of transcatheter arterial chemoembolization and sorafenib is well tolerated and effective in Asian patients with hepatocellular carcinoma:Final results of the START trial[J].Int J Cancer, 2015, 136 (6) :1458-1467.
    [22]WU FQ, FANG T, YU LX, et al.ADRB2 signaling promotes HCC progression and sorafenib resistance by inhibiting autophagic degradation of HIF1α[J].J Hepatol, 2016, 65 (2) :314-324.
    [23]FENG F, JIANG Q, CAO S, et al.Pregnane X receptor mediates sorafenib resistance in advanced hepatocellular carcinoma[J].Biochim Biophys Acta, 2018, 1862 (4) :1017-1030.
    [24]SIEGEL AB, COHEN EI, OCEAN A, et al.Phase II trial evaluating the clinical and biologic effects of bevacizumab in unresectable hepatocellular carcinoma[J].J Clin Oncol, 2008, 26 (18) :2992-2998.
    [25]de PASQUALE MD, de VILLE de GOYET J, MONTI L, et al.Bevacizumab combined with chemotherapy in children affected by hepatocellular carcinoma:A single-center experience[J].Anticancer Res, 2017, 37 (3) :1489-1493.
    [26]ZHU AX, BLASZKOWSKY LS, RYAN DP, et al.Phase II study of gemcitabine and oxaliplatin in combination with bevacizumab in patients with advanced hepatocellular carcinoma[J].J Clin Oncol, 2006, 24 (12) :1898-1903.
    [27]SUN W, SOHAL D, HALLER DG, et al.Phase 2 trial of bevacizumab, capecitabine, and oxaliplatin in treatment of advancedhepatocellular carcinoma[J].Cancer, 2011, 117 (14) :3187-3192.
    [28]KASEB AO, MORRIS JS, IWASAKI M, et al.Phase II trial of bevacizumab and erlotinib as a second-line therapy for advanced hepatocellular carcinoma[J].Onco Targets Ther, 2016, 9 (Suppl 4) :773-780.
    [29]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) [J].Target Oncol, 2017, 12 (2) :201-209.
    [30]TOH HC, CHEN PJ, CARR BI, et al.Phase 2 trial of linifanib (ABT-869) in patients with unresectable or metastatic hepatocellular carcinoma[J].Cancer, 2013, 119 (2) :380-387.
    [31]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].J Clin Oncol, 2015, 33 (2) :172-179.
    [32]CUCCHETTI A, PISCAGLIA F, PINNA AD, et al.Efficacy and safety of systemic therapies for advanced hepatocellular carcinoma:A network meta-analysis of phase III trials[J].Liver Cancer, 2017, 6 (4) :337-348.
    [33]YU WC, ZHANG KZ, CHEN SG, et al.Efficacy and safety of apatinib in patients with intermediate/advanced hepatocellular carcinoma:A prospective observation study[J].Medicine (Baltimore) , 2018, 97 (3) :e9704.
    [34]KONG Y, SUN L, HOU Z, et al.Apatinib is effective for treatment of advanced hepatocellular carcinoma[J].Oncotarget, 2017, 8 (62) :105596-105605.
    [35] 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[J].Lancet, 2017, 389 (10064) :56-66.
    [36]PELOSOF L, LEMERY S, CASAK S, et al.Benefit-risk summary of regorafenib for the treatment of patients with advanced hepatocellular carcinoma that has progressed on sorafenib[J].Oncologist, 2018, 23 (4) :496-500.
    [37]BOUATTOUR M, RAYMOND E, QIN S, et al.Recent developments of c-Met as a therapeutic target in hepatocellular carcinoma[J].Hepatology, 2018, 67 (3) :1132-1149.
    [38]SANTORO A, RIMASSA L, BORBATH I, et al.tivantinib for second-line treatment of advanced hepatocellular carcinoma:A randomised, placebo-controlled phase 2 study[J].Lancet Oncol, 2013, 14 (1) :55-63.
    [39] RIMASSA L, ABBADESSA G, PERSONENI N, et al.Tumor and circulating biomarkers in patients with second-line hepatocellular carcinoma from the randomized phase II study with tivantinib[J].Oncotarget, 2016, 7 (45) :72622-72633.
    [40]PINEDA E, SALUD A, VILA-NAVARRO E, et al.Dynamic soluble changes in s VEGFR1, HGF, and VEGF promote chemotherapy and bevacizumab resistance:A prospective translational study in the BECOX (GEMCAD 09-01) trial[J].Tumour Biol, 2017, 39 (6) :1010428317705509.
    [41]ABOU-ALFA G, CHENG AL, MEYER T, et al.Phase 3 randomized, double-blind, controlled study of cabozantinib (XL184) versus placebo in subjects with hepatocellular carcinoma who have received prior sorafenib (CELESTIAL;NCT01908426) [J].J Clin Oncol, 2014, 32 (15 Suppl) :TPS4150.
    [42]HAN P, LI H, JIANG X, et al.Dual inhibition of Akt and c-Met as a second-line therapy following acquired resistance to sorafenib in hepatocellular carcinoma cells[J].Mol Oncol, 2017, 11 (3) :320-334.
    [43]KOEBERLE D, DUFOUR JF, DEMETER G, 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) [J].Ann Oncol, 2016, 27 (5) :856-861.
    [44]GEISSLER EK, SCHNITZBAUER AA, ZULKE C, et al.Sirolimus use in liver transplant recipients with hepatocellular carcinoma:A randomized, multicenter, open-label phase 3 trial[J].Transplantation, 2016, 100 (1) :116-125.
    [45]HAYASHI T, YAMASHITA T, OKADA H, et al.A novel m TOR inhibitor;anthracimycin for the treatment of human hepatocellular carcinoma[J].Anticancer Res, 2017, 37 (7) :3397-3403.
    [46]ZHANG W, CHEN B, ZHANG Y, et al.The anti-hepatocellular carcinoma cell activity by a novel m TOR kinase inhibitor CZ415[J].Biochem Biophys Res Commun, 2017, 487 (3) :494-499.
    [47]KIM JO, KIM KH, SONG IS, et al.Potentiation of the anticancer effects of everolimus using a dual m TORC1/2 inhibitor in hepatocellular carcinoma cells[J].Oncotarget, 2017, 8 (2) :2936-2948.
    [48]PIVONELLO C, NEGRI M, de MARTINO MC, et al.The dual targeting of insulin and insulin-like growth factor 1 receptor enhances the m TOR inhibitor-mediated antitumor efficacy in hepatocellular carcinoma[J].Oncotarget, 2016, 7 (9) :9718-9731.
    [49]TSUJI-TAMURA K, OGAWA M.Dual inhibition of m TORC1 and m TORC2 perturbs cytoskeletal organization and impairs endothelial cell elongation[J].Biochem Biophys Res Commun, 2018, 497 (1) :326-331.
    [50]FENG D, HUI X, SHI-CHUN L, et al.Initial experience of anti-PD1 therapy with nivolumab in advanced hepatocellular carcinoma[J].Oncotarget, 2017, 8 (57) :96649-96655.
    [51]EL-KHOUEIRY AB, SANGRO B, YAU T, et al.Nivolumab in patients with advanced hepatocellular carcinoma (Check Mate 040) :An open-label, non-comparative, phase 1/2 dose escalation and expansion trial[J].Lancet, 2017, 389 (10088) :2492-2502.
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