磷脂酰肌醇蛋白聚糖-3靶向治疗肝细胞癌的研究进展

方宇昕; 李育; 刘宝姝; 董国强; 方宇昕; 李育; 刘宝姝; 董国强

doi:10.12206/j.issn.2097-2024.202307047

[1]

BRAY F, FERLAY J, SOERJOMATARAM I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6):394-424. doi: 10.3322/caac.21492

[2]

VOGEL A, MEYER T, SAPISOCHIN G, et al. Hepatocellular carcinoma[J]. Lancet, 2022, 400(10360):1345-1362. doi: 10.1016/S0140-6736(22)01200-4

[3]

LLOVET J M, RICCI S, MAZZAFERRO V, et al. Sorafenib in advanced hepatocellular carcinoma[J]. N Engl J Med, 2008, 359(4):378-390. doi: 10.1056/NEJMoa0708857

[4]

HO M, KIM H. Glypican-3: a new target for cancer immunotherapy[J]. Eur J Cancer, 2011, 47(3): 333-338.

[5]

FILMUS J, SELLECK S B. Glypicans: proteoglycans with a surprise[J]. J Clin Invest, 2001, 108(4):497-501. doi: 10.1172/JCI200113712

[6]

IGLESIAS B V, CENTENO G, PASCUCCELLI H, et al. Expression pattern of glypican-3 (GPC3) during human embryonic and fetal development[J]. Histol Histopathol, 2008, 23(11):1333-1340.

[7]

CAPURRO M, WANLESS IR, FILUMS J, et al. Glypican-3: a novel serum and histochemical marker for hepatocellular carcinoma[J]. Gastroenterology, 2003, 125(1):89-97. doi: 10.1016/S0016-5085(03)00689-9

[8]

PEZ F, LOPEZ A, MERLE P, et al. Wnt signaling and hepatocarcinogenesis: molecular targets for the development of innovative anticancer drugs[J]. J Hepatol, 2013, 59(5):1107-1117. doi: 10.1016/j.jhep.2013.07.001

[9]

BENGOCHEA A, DE SOUZA M M, LEFRANÇOIS L, et al. Common dysregulation of Wnt/Frizzled receptor elements in human hepatocellular carcinoma[J]. Br J Cancer, 2008, 99(1):143-150. doi: 10.1038/sj.bjc.6604422

[10]

ANASTAS J N, MOON R T. WNT signalling pathways as therapeutic targets in cancer[J]. Nat Rev Cancer, 2013, 13(1):11-26. doi: 10.1038/nrc3419

[11]

CONG F, SCHWEIZER L, VARMUS H. Wnt signals across the plasma membrane to activate the β-catenin pathway by forming oligomers containing its receptors, Frizzled and LRP[J]. Development, 2004, 131(20):5103-5115. doi: 10.1242/dev.01318

[12]

ZENG X, TAMAI K, DOBLE B, et al. A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation[J]. Nature, 2005, 438(7069): 873-877.

[13]

GAO C, CHEN Y G. Dishevelled: the hub of Wnt signaling[J]. Cell Signal, 2010, 22(5):717-727. doi: 10.1016/j.cellsig.2009.11.021

[14]

VLAD A, ROHTS S, MULLER O, et al. The first five years of the Wnt targetome[J]. Cell Signal, 2008, 20(5):795-802. doi: 10.1016/j.cellsig.2007.10.031

[15]

CAPURRO M I, XIANG Y Y, LOBE C, et al. Glypican-3 promotes the growth of hepatocellular carcinoma by stimulating canonical Wnt signaling[J]. Cancer Res, 2005, 65(14):6245-6254. doi: 10.1158/0008-5472.CAN-04-4244

[16]

DE CAT B, MUYLDERMANS S Y, COOMANS C, et al. Processing by proprotein convertases is required for glypican-3 modulation of cell survival, Wnt signaling, and gastrulation movements[J]. J Cell Biol, 2003, 163(3):625-635. doi: 10.1083/jcb.200302152

[17]

LEE K P, LEE J H, KIM T S, et al. The Hippo-Salvador pathway restrains hepatic oval cell proliferation, liver size, and liver tumorigenesis[J]. Proc Natl Acad Sci USA, 2010, 107(18):8248-8253. doi: 10.1073/pnas.0912203107

[18]

PAN DJ. The hippo signaling pathway in development and cancer[J]. Dev Cell, 2010, 19(4):491-505. doi: 10.1016/j.devcel.2010.09.011

[19]

LI H, WOLFE A, SEPTER S, et al. Deregulation of Hippo kinase signalling in human hepatic malignancies[J]. Liver Int, 2012, 32(1):38-47. doi: 10.1111/j.1478-3231.2011.02646.x

[20]

MIAO H L, PAN Z J, LEI C J, et al. Knockdown of GPC3 inhibits the proliferation of Huh7 hepatocellular carcinoma cells through down-regulation of YAP[J]. J Cell Biochem, 2013, 114(3):625-631. doi: 10.1002/jcb.24404

[21]

FILMUS J, CAPURRO M. The role of glypicans in hedgehog signaling[J]. Matrix Biol, 2014, 35: 248-252.

[22]

DING M, WANG X. Antagonism between hedgehog and Wnt signaling pathways regulates tumorigenicity (review)[J]. Oncol Lett, 2017,14(6):6327-6333.

[23]

CHATTERJEE S, SIL P C. Targeting the crosstalks of Wnt pathway with Hedgehog and Notch for cancer therapy[J]. Pharmacol Res, 2019, 142:251-261. doi: 10.1016/j.phrs.2019.02.027

[24]

MATSUI W H. Cancer stem cell signaling pathways[J]. Medicine, 2016, 95(1 Suppl 1): S8-S19.

[25]

CAPURRO MI, XU P, FILMUS J, et al. Glypican-3 inhibits hedgehog signaling during development by competing with patched for hedgehog binding[J]. Dev Cell, 2008, 14(5):700-711. doi: 10.1016/j.devcel.2008.03.006

[26]

WANG S S, CHEN N, CHEN Y H, et al. Elevated GPC3 level promotes cell proliferation in liver cancer[J]. Oncol Lett, 2018, 16(1):970-976.

[27]

MIDORIKAWA Y, ISHIKAWA S, IWANARI H, et al. Glypican-3, overexpressed in hepatocellular carcinoma, modulates FGF₂ and BMP-7 signaling[J]. Int J Cancer, 2003, 103(4):455-465. doi: 10.1002/ijc.10856

[28]

AKUTSU N, YAMAMOTO H, SASAKI S, et al. Association of glypican-3 expression with growth signaling molecules in hepatocellular carcinoma[J]. World J Gastroenterol, 2010, 16(28):3521-3528. doi: 10.3748/wjg.v16.i28.3521

[29]

ACEVEDO V D, ITTMANN M, SPENCER D M. Paths of FGFR-driven tumorigenesis[J]. Cell Cycle, 2009, 8(4):580-588. doi: 10.4161/cc.8.4.7657

[30]

Song H H, SHI W, FILMUS J, et al. OCI-5/rat glypican-3 binds to fibroblast growth factor-2 but not to insulin-like growth factor-2[J]. J Biol Chem, 1997, 272(12):7574-7577. doi: 10.1074/jbc.272.12.7574

[31]

LAI J P, SANDHU D S, YU C R, et al. Sulfatase 2 up-regulates glypican 3, promotes fibroblast growth factor signaling, and decreases survival in hepatocellular carcinoma[J]. Hepatology, 2008, 47(4):1211-1222. doi: 10.1002/hep.22202

[32]

KAPOSI-NOVAK P, LEE J S, GÒMEZ-QUIROZ L, et al. Met-regulated expression signature defines a subset of human hepatocellular carcinomas with poor prognosis and aggressive phenotype[J]. J Clin Invest, 2006, 116(6):1582-1595. doi: 10.1172/JCI27236

[33]

SUN C K, CHUA M S, HE J, et al. Suppression of glypican 3 inhibits growth of hepatocellular carcinoma cells through up-regulation of TGF-β2[J]. Neoplasia, 2011, 13(8):735-747. doi: 10.1593/neo.11664

[34]

ISHIGURO T, SUGIMOTO M, KINOSHITA Y, et al. Anti-glypican 3 antibody as a potential antitumor agent for human liver cancer[J]. Cancer Res, 2008, 68(23): 9832-9838.

[35]

ZHU A X, GOLD P J, EL-KHOUEIRY A B, et al. First-in-man phase I study of GC33, a novel recombinant humanized antibody against glypican-3, in patients with advanced hepatocellular carcinoma[J]. Clin Cancer Res, 2013, 19(4): 920-928.

[36]

IKEDA M, OHKAWA S, OKUSAKA T, et al. Japanese phase I study ofGC 33, a humanized antibody against glypican-3 for advanced hepatocellular carcinoma[J]. Cancer Sci, 2014, 105(4):455-462. doi: 10.1111/cas.12368

[37]

GHASSAN K, Abou-Alfa. Randomized phase II placebo controlled study of codrituzumab in previously treated patients with advanced hepatocellular carcinoma[J]. J Hepatol, 2016, 65(2):289-295. doi: 10.1016/j.jhep.2016.04.004

[38]

LIU X Y, GAO F, JIANG L W, et al. 32A9, a novel human antibody for designing an immunotoxin and CAR-T cells against glypican-3 in hepatocellular carcinoma[J]. J Transl Med, 2020, 18(1):295. doi: 10.1186/s12967-020-02462-1

[39]

FENG M Q, GAO W, WANG R Q, et al. Therapeutically targeting glypican-3 via a conformation-specific single-domain antibody in hepatocellular carcinoma[J]. Proc Natl Acad Sci USA, 2013, 110(12):E1083-E1091.

[40]

GAO W, KIM H, FENG M Q, et al. Inactivation of Wnt signaling by a human antibody that recognizes the heparan sulfate chains of glypican-3 for liver cancer therapy[J]. Hepatology, 2014, 60(2):576-587. doi: 10.1002/hep.26996

[41]

SHIRAIWA H, NARITA A, IGAWA T, et al. Engineering a bispecific antibody with a common light chain: identification and optimization of an anti-CD3 epsilon and anti-GPC3 bispecific antibody, ERY974[J]. Methods, 2019, 154:10-20. doi: 10.1016/j.ymeth.2018.10.005

[42]

ISHIGURO T, SANO Y, KOMATSU S I, et al. An anti-glypican 3/CD3 bispecific T cell-redirecting antibody for treatment of solid tumors[J]. Sci Transl Med, 2017, 9(410):eaal4291. doi: 10.1126/scitranslmed.aal4291

[43]

DU K X, LI Y L, LIU J, et al. A bispecific antibody targeting GPC3 and CD47 induced enhanced antitumor efficacy against dual antigen-expressing HCC[J]. Mol Ther, 2021, 29(4):1572-1584. doi: 10.1016/j.ymthe.2021.01.006

[44]

NAKATSURA T, KOMORI H, KUBO T, et al. Mouse homologue of a novel human oncofetal antigen, glypican-3, evokes T-cell-mediated tumor rejection without autoimmune reactions in mice[J]. Clin Cancer Res, 2004, 10(24):8630-8640. doi: 10.1158/1078-0432.CCR-04-1177

[45]

KOMORI H, NAKATSURA T, SENJU S, et al. Identification of HLA-A2- or HLA-A24-restricted CTL epitopes possibly useful for glypican-3-specific immunotherapy of hepatocellular carcinoma[J]. Clin Cancer Res, 2006, 12(9):2689-2697. doi: 10.1158/1078-0432.CCR-05-2267

[46]

SAWADA Y, YOSHIKAWA T, NOBUOKA D, et al. Phase I trial of a glypican-3-derived peptide vaccine for advanced hepatocellular carcinoma: immunologic evidence and potential for improving overall survival[J]. Clin Cancer Res, 2012, 18(13):3686-3696. doi: 10.1158/1078-0432.CCR-11-3044

[47]

SAWADA Y, YOSHIKAWA T, OFUJI K, et al. Phase II study of the GPC3-derived peptide vaccine as an adjuvant therapy for hepatocellular carcinoma patients[J]. Oncoimmunology, 2016, 5(5):e1129483. doi: 10.1080/2162402X.2015.1129483

[48]

SAYEM M A, TOMITA Y, YUNO A, et al. Identification of glypican-3-derived long peptides activating both CD8⁺ and CD4⁺ T cells; prolonged overall survival in cancer patients with Th cell response[J]. Oncoimmunology, 2015, 5(1): e1062209.

[49]

LI S Q, LIN J, QI C Y, et al. GPC3 DNA vaccine elicits potent cellular antitumor immunity against HCC in mice[J]. Hepato-gastroenterology, 2014, 61(130):278-284.

[50]

SAWADA Y, YOSHIKAWA T, SHIMOMURA M, et al. Programmed death-1 blockade enhances the antitumor effects of peptide vaccine-induced peptide-specific cytotoxic T lymphocytes[J]. Int J Oncol, 2015, 46(1):28-36. doi: 10.3892/ijo.2014.2737

[51]

PASTAN I, HASSAN R, FITZGERALD D J, et al. Immunotoxin therapy of cancer[J]. Nat Rev Cancer, 2006, 6(7):559-565. doi: 10.1038/nrc1891

[52]

GAO W, TANG Z W, ZHANG Y F, et al. Immunotoxin targeting glypican-3 regresses liver cancer via dual inhibition of Wnt signalling and protein synthesis[J]. Nat Commun, 2015, 6:6536. doi: 10.1038/ncomms7536

[53]

WANG C G, GAO W, FENG M Q, et al. Construction of an immunotoxin, HN₃-mPE24, targeting glypican-3 for liver cancer therapy[J]. Oncotarget, 2017, 8(20):32450-32460. doi: 10.18632/oncotarget.10592

[54]

FLEMING B D, URBAN D J, HALL M D, et al. Engineered anti-GPC3 immunotoxin, HN₃-ABD-T20, produces regression in mouse liver cancer xenografts through prolonged serum retention[J]. Hepatology, 2020, 71(5):1696-1711. doi: 10.1002/hep.30949

[55]

PORTER D L, HWANG W T, FREY N V, et al. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia[J]. Sci Transl Med, 2015, 7(303):303ra139.

[56]

WU XQ, LUO H, LI ZH, et al. Combined antitumor effects of sorafenib and GPC3-CAR T cells in mouse models of hepatocellular carcinoma[J]. Mol Ther, 2019, 27(8):1483-1494. doi: 10.1016/j.ymthe.2019.04.020

[57]

LI K S, QIAN S Y, HUANG M M, et al. Development of GPC3 and EGFR-dual-targeting chimeric antigen receptor-T cells for adoptive T cell therapy[J]. Am J Transl Res, 2021, 13(1): 156-167.

[58]

YU M, LUO H, LI ZH, et al. Development of GPC3-specific chimeric antigen receptor-engineered natural killer cells for the treatment of hepatocellular carcinoma[J]. Mol Ther, 2018, 26(2):366-378. doi: 10.1016/j.ymthe.2017.12.012

[59]

MAUREL M, JALVY S, LADEIRO Y, et al. A functional screening identifies five micrornas controlling glypican-3: role of mir-1271 down-regulation in hepatocellular carcinoma[J]. Hepatology, 2013, 57(1):195-204. doi: 10.1002/hep.25994

[60]

LUO R C. Inhibition of glypican-3 expression via RNA interference influences the growth and invasive ability of the MHCC97-H human hepatocellular carcinoma cell line[J]. Int J Mol Med, 2011,28(4):497-503.

[61]

YU D D, DONG Z Z, YAO M, et al. Targeted glypican-3 gene transcription inhibited the proliferation of human hepatoma cells by specific short hairpin RNA[J]. Tumor Biol, 2013, 34(2):661-668. doi: 10.1007/s13277-012-0593-y

[62]

LIU S Y, LI Y M, CHEN W, et al. Silencing glypican-3 expression induces apoptosis in human hepatocellular carcinoma cells[J]. Biochem Biophys Res Commun, 2012, 419(4):656-661. doi: 10.1016/j.bbrc.2012.02.069

[63]

WANG K, KIEVIT F M, SHAM J G, et al. Iron-oxide-based nanovector for tumor targeted siRNA delivery in an orthotopic hepatocellular carcinoma xenograft mouse model[J]. Small, 2016, 12(4):477-487. doi: 10.1002/smll.201501985

[64]

ENDO M, KINOSHITA Y, ADACHI K, et al. Abstract 2747: Anti-glypican-3 monoclonal antibody (codrituzumab/GC33/RO5137382) treatment enhances tumor infiltration of PD-L1-positive macrophages, and combination therapy with anti-PD-L1 monoclonal antibody promotes antitumor effects[J]. Cancer Res, 2018, 78(13_Supplement):2747. doi: 10.1158/1538-7445.AM2018-2747

[65]

IOKA T, KANAI M, KOBAYASHI S, et al. Randomized phase III study of gemcitabine, cisplatin plus S-1 versus gemcitabine, cisplatin for advanced biliary tract cancer (KHBO1401- MITSUBA)[J]. J Hepatobiliary Pancreat Sci, 2023, 30(1):102-110. doi: 10.1002/jhbp.1219

[66]

BASKARAN R, LEE J, YANG S G. Clinical development of photodynamic agents and therapeutic applications[J]. Biomater Res, 2018, 22:25. doi: 10.1186/s40824-018-0140-z

[67]

HU J H, SHI J L, GAO Y Q, et al. 808 nm near-infrared light-excited UCNPs@mSiO₂-Ce6-GPC3 nanocomposites for photodynamic therapy in liver cancer[J]. Int J Nanomed, 2019, 14:10009-10021. doi: 10.2147/IJN.S221496

[68]

LIU Y L, TAN M M, FANG C J, et al. A novel multifunctional gold nanorod-mediated and tumor-targeted gene silencing of GPC-3 synergizes photothermal therapy for liver cancer[J]. Nanotechnology, 2021, 32(17):175101. doi: 10.1088/1361-6528/abdbed