中文｜English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 41 Issue 10
Oct.  2025
Turn off MathJax
Article Contents
Article Navigation >  Journal of Clinical Hepatology  > 2025  >  41(10): 2154-2160

Mechanism of radiotherapy resistance in hepatocellular carcinoma and related coping strategies

DOI: 10.12449/JCH251029
  • 1.

    Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University，Chongqing 400010，China

  • 2.

    Institute of Infection and Hepatology, The Second Affiliated Hospital of Chongqing Medical University，Chongqing 400010，China

Research funding:

Chongqing Science Fund for Distinguished Young Scholars (CSTB2022NSCQ-JQX0032);

Program for Youth Innovation in Future Medicine of Chongqing Medical University (W0156)

More Information
  • Corresponding author: WU Chuanxin， 300395@cqmu.edu.cn （ORCID： 0000-0002-1481-2582）
  • Received Date: 2025-03-01
  • Accepted Date: 2025-05-06
  • Published Date: 2025-10-25
    Abstract
  • Primary liver cancer is a malignant tumor with continuously rising incidence and mortality rates worldwide， imposing a heavy burden on patients and society， and hepatocellular carcinoma （HCC） is a common type of primary liver cancer. As one of the important treatment methods for HCC， radiotherapy can effectively control the local growth of tumors and alleviate symptoms in patients. However， radiotherapy resistance seriously affects the treatment effect and has become a major challenge in clinical treatment. Current research shows a complex mechanism of radiotherapy resistance in HCC， involving multiple factors such as abnormal activation of intracellular signaling pathways， changes in tumor microenvironment， and regulation of gene expression. Therefore， a series of strategies have been proposed to address radiotherapy resistance in clinical practice， including regulating cell signaling pathways， improving tumor microenvironment， and combining different treatment modalities， and such strategies have shown promising application prospects. This article reviews the research advances in the mechanism of radiotherapy resistance and related coping strategies， in order to provide new perspectives for future research on radiotherapy for HCC.

     

    • FullText(HTML)
  • loading
    • References(44)
  • [1]
    CHEN WQ, CHIANG CL, DAWSON LA. Efficacy and safety of radiotherapy for primary liver cancer[J]. Chin Clin Oncol, 2021, 10( 1): 9. DOI: 10.21037/cco-20-89.
    [2]
    ZHANG CH, CHENG YF, ZHANG S, et al. Changing epidemiology of hepatocellular carcinoma in Asia[J]. Liver Int, 2022, 42( 9): 2029- 2041. DOI: 10.1111/liv.15251.
    [3]
    ZHANG ZZ, WANG MX, WU YF, et al. Epidemiological and clinical characteristics of hepatocellular carcinoma in Xiamen[J]. Cancer Epidemiol, 2024, 93: 102691. DOI: 10.1016/j.canep.2024.102691.
    [4]
    CAPASSO M, COSSIGA V, GUARINO M, et al. The role of hepatitis viruses as drivers of hepatocancerogenesis[J]. Cancers, 2024, 16( 8): 1505. DOI: 10.3390/cancers16081505.
    [5]
    ZHANG H, FU Y, TAN BB, et al. Clinical application and progress of yttrium 90 microsphere selective internal radiation therapy in primary hepatic cancer[J]. Chin J Dig Surg, 2024, 23( 2): 242- 247. DOI: 10.3760/cma.j.cn115610-20231208-00242.

    张辉, 付颖, 谭斌彬, 等. 钇-90微球选择性内放射治疗在原发性肝癌中的临床应用及进展[J]. 中华消化外科杂志, 2024, 23( 2): 242- 247. DOI: 10.3760/cma.j.cn115610-20231208-00242.
    [6]
    FANG ZY, JIN S, LI G. Efficacy and prognostic factors of intensity-modulated radiotherapy for large primary hepatocellular carcinoma[J]. J Clin Hepatol, 2015, 31( 6): 886- 890. DOI: 10.3969/j.issn.1001-5256.2015.06.014.

    方子燕, 金帅, 黎功. 原发性大肝癌调强放疗的疗效及预后分析[J]. 临床肝胆病杂志, 2015, 31( 6): 886- 890. DOI: 10.3969/j.issn.1001-5256.2015.06.014.
    [7]
    CUNEO KC, HERR DJ. Advances in radiation therapy for primary liver cancer[J]. Surg Oncol Clin N Am, 2023, 32( 3): 415- 432. DOI: 10.1016/j.soc.2023.02.002.
    [8]
    DIONISI F, SCARTONI D, FRACCHIOLLA F, et al. Proton therapy in the treatment of hepatocellular carcinoma[J]. Front Oncol, 2022, 12: 959552. DOI: 10.3389/fonc.2022.959552.
    [9]
    LING R, WANG JZ, FANG Y, et al. HDAC-an important target for improving tumor radiotherapy resistance[J]. Front Oncol, 2023, 13: 1193637. DOI: 10.3389/fonc.2023.1193637.
    [10]
    JAGASIA S, TASCI E, ZHUGE Y, et al. Identifying patients suitable for targeted adjuvant therapy: Advances in the field of developing biomarkers for tumor recurrence following irradiation[J]. Expert Rev Precis Med Drug Dev, 2023, 8( 1): 33- 42. DOI: 10.1080/23808993.2023.2276927.
    [11]
    MIR SM, ALIARAB A, GOODARZI G, et al. Melatonin: A smart molecule in the DNA repair system[J]. Cell Biochem Funct, 2022, 40( 1): 4- 16. DOI: 10.1002/cbf.3672.
    [12]
    HUANG CY, LAI ZY, HSU TJ, et al. Boron neutron capture therapy eliminates radioresistant liver cancer cells by targeting DNA damage and repair responses[J]. J Hepatocell Carcinoma, 2022, 9: 1385- 1401. DOI: 10.2147/jhc.s383959.
    [13]
    BYUN HK, KIM C, SEONG J. Carbon ion radiotherapy in the treatment of hepatocellular carcinoma[J]. Clin Mol Hepatol, 2023, 29( 4): 945- 957. DOI: 10.3350/cmh.2023.0217.
    [14]
    BEDOLLA N, LIU L, XIE Q, et al. Quercetin regulates sensitivity to X-ray radiation of hepatocellular carcinoma through miR-216a-3p[J]. Biomol Biomed, 2025, 25( 4): 833- 849. DOI: 10.17305/bb.2024.11125.
    [15]
    JIN Q, HU H, YAN SQ, et al. lncRNA MIR22HG-derived miR-22-5p enhances the radiosensitivity of hepatocellular carcinoma by increasing histone acetylation through the inhibition of HDAC2 activity[J]. Front Oncol, 2021, 11: 572585. DOI: 10.3389/fonc.2021.572585.
    [16]
    JIA HJ, WEI PK, ZHOU SJ, et al. Attenuated Salmonella carrying siRNA-PD-L1 and radiation combinatorial therapy induces tumor regression on HCC through T cell-mediated immuno-enhancement[J]. Cell Death Discov, 2023, 9: 318. DOI: 10.1038/s41420-023-01603-x.
    [17]
    JENG KS, CHANG CF, SHEEN IS, et al. Cellular and molecular biology of cancer stem cells of hepatocellular carcinoma[J]. Int J Mol Sci, 2023, 24( 2): 1417. DOI: 10.3390/ijms24021417.
    [18]
    KABAKOV AE, YAKIMOVA AO. Hypoxia-induced cancer cell responses driving radioresistance of hypoxic tumors: Approaches to targeting and radiosensitizing[J]. Cancers, 2021, 13( 5): 1102. DOI: 10.3390/cancers13051102.
    [19]
    WEI HJ, WANG CR, CROCE CM, et al. p62/SQSTM1 synergizes with autophagy for tumor growth in vivo[J]. Genes Dev, 2014, 28( 11): 1204- 1216. DOI: 10.1101/gad.237354.113.
    [20]
    KIM W, LEE S, SEO D, et al. Cellular stress responses in radiotherapy[J]. Cells, 2019, 8( 9): 1105. DOI: 10.3390/cells8091105.
    [21]
    YAO QW, ZHENG R, XIE GZ, et al. Late-responding normal tissue cells benefit from high-precision radiotherapy with prolonged fraction delivery times via enhanced autophagy[J]. Sci Rep, 2015, 5: 9119. DOI: 10.1038/srep09119.
    [22]
    ZHENG W, SHEN GL, XU KY, et al. Lnc524369 promotes hepatocellular carcinoma progression and predicts poor survival by activating YWHAZ-RAF1 signaling[J]. World J Gastrointest Oncol, 2022, 14( 1): 253- 264. DOI: 10.4251/wjgo.v14.i1.253.
    [23]
    SAKAGUCHI H, TSUCHIYA H, KITAGAWA Y, et al. NEAT1 confers radioresistance to hepatocellular carcinoma cells by inducing autophagy through GABARAP[J]. Int J Mol Sci, 2022, 23( 2): 711. DOI: 10.3390/ijms23020711.
    [24]
    DAI XF, WANG DJ, ZHANG JY. Programmed cell death, redox imbalance, and cancer therapeutics[J]. Apoptosis, 2021, 26( 7-8): 385- 414. DOI: 10.1007/s10495-021-01682-0.
    [25]
    GHAHREMANIFARD P, CHANDA A, BONNI S, et al. TGF-β mediated immune evasion in cancer-spotlight on cancer-associated fibroblasts[J]. Cancers(Basel), 2020, 12( 12): 3650. DOI: 10.3390/cancers12123650.
    [26]
    CUKIERMAN E. A reflection on how carcinoma-associated fibroblasts were recognized as active participants of epithelial tumorigenesis[J]. Cancer Res, 2021, 81( 18): 4668- 4670. DOI: 10.1158/0008-5472.CAN-21-2553.
    [27]
    KIM TW. Fisetin, an anti-inflammatory agent, overcomes radioresistance by activating the PERK-ATF4-CHOP axis in liver cancer[J]. Int J Mol Sci, 2023, 24( 10): 9076. DOI: 10.3390/ijms24109076.
    [28]
    XU YY, CHEN YH, JIN J, et al. Modulating tumour vascular normalisation using triptolide-loaded NGR-functionalized liposomes for enhanced cancer radiotherapy[J]. J Liposome Res, 2023, 33( 3): 251- 257. DOI: 10.1080/08982104.2022.2161095.
    [29]
    LIANG HZ, SHEN XL. LXR activation radiosensitizes non-small cell lung cancer by restricting myeloid-derived suppressor cells[J]. Biochem Biophys Res Commun, 2020, 528( 2): 330- 335. DOI: 10.1016/j.bbrc.2020.04.137.
    [30]
    MCANDREWS KM, CHEN Y, DARPOLOR JK, et al. Identification of functional heterogeneity of carcinoma-associated fibroblasts with distinct IL6-mediated therapy resistance in pancreatic cancer[J]. Cancer Discov, 2022, 12( 6): 1580- 1597. DOI: 10.1158/2159-8290.CD-20-1484.
    [31]
    DUNLOCK VE. Tetraspanin CD53: An overlooked regulator of immune cell function[J]. Med Microbiol Immunol, 2020, 209( 4): 545- 552. DOI: 10.1007/s00430-020-00677-z.
    [32]
    DAWSON HD, SANG YM, LUNNEY JK. Porcine cytokines, chemokines and growth factors: 2019 update[J]. Res Vet Sci, 2020, 131: 266- 300. DOI: 10.1016/j.rvsc.2020.04.022.
    [33]
    LIU C, LIU XM, ZHOU HY, et al. Growth factors and cytokines involved in liver regeneration[J]. Eur Cytokine Netw, 2023, 34( 4): 38- 45. DOI: 10.1684/ecn.2023.0483.
    [34]
    WANG YH, CHEN ZM, YIN YC, et al. Mechanism and application progress of sensitivity regulation of tumor associated macrophages in radiotherapy[J]. Trauma Crit Care Med, 2024, 12( 3): 182- 185, 190. DOI: 10.16048/j.issn.2095-5561.2024.03.13.

    王禹杭, 陈志明, 殷雨成, 等. 肿瘤相关巨噬细胞放射治疗敏感性调节机制与应用进展[J]. 创伤与急危重病医学, 2024, 12( 3): 182- 185, 190. DOI: 10.16048/j.issn.2095-5561.2024.03.13.
    [35]
    PENG C, XU YL, WU J, et al. TME-related biomimetic strategies against cancer[J]. Int J Nanomed, 2024, 19: 109- 135. DOI: 10.2147/ijn.s441135.
    [36]
    ZHAO W, HU H, MO Q, et al. Function and mechanism of combined PARP-1 and BRCA genes in regulating the radiosensitivity of breast cancer cells[J]. Int J Clin Exp Pathol, 2019, 12( 10): 3915- 3920.
    [37]
    SATO H, OKONOGI N, NAKANO T. Rationale of combination of anti-PD-1/PD-L1 antibody therapy and radiotherapy for cancer treatment[J]. Int J Clin Oncol, 2020, 25( 5): 801- 809. DOI: 10.1007/s10147-020-01666-1.
    [38]
    YANG YJ, KE TY, LIU SX, et al. Synergistic sensitization of apatinib mesylate and radiotherapy on hepatocarcinoma cells in vitro[J]. J Jilin Univ(Med Ed), 2024, 50( 4): 1009- 1015. DOI: 10.13481/j.1671-587X.202404015.

    杨永净, 柯天洋, 刘士新, 等. 甲磺酸阿帕替尼联合放疗对肝癌HepG2细胞的体外协同增敏作用[J]. 吉林大学学报(医学版), 2024, 50( 4): 1009- 1015. DOI: 10.13481/j.1671-587X.202404015.
    [39]
    CHEN YH, WEI MF, WANG CW, et al. Dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor is an effective radiosensitizer for colorectal cancer[J]. Cancer Lett, 2015, 357( 2): 582- 590. DOI: 10.1016/j.canlet.2014.12.015.
    [40]
    YOSHIDA A, KITAYAMA Y, HAYAKAWA N, et al. Biocompatible polymer-modified gold nanocomposites of different shapes as radiation sensitizers[J]. Biomater Sci, 2022, 10( 10): 2665- 2672. DOI: 10.1039/d2bm00174h.
    [41]
    SEBASTIAN AM, PETER D. Artificial intelligence in cancer research: Trends, challenges and future directions[J]. Life, 2022, 12( 12): 1991. DOI: 10.3390/life12121991.
    [42]
    BORCZYK M, PIECHOTA M, RODRIGUEZ PARKITNA J, et al. Prospects for personalization of depression treatment with genome sequencing[J]. Br J Pharmacol, 2022, 179( 17): 4220- 4232. DOI: 10.1111/bph.15470.
    [43]
    HORLAIT M, BAES S, DE REGGE M, et al. Understanding the complexity, underlying processes, and influencing factors for optimal multidisciplinary teamwork in hospital-based cancer teams: A systematic integrative review[J]. Cancer Nurs, 2021, 44( 6): E476- E492. DOI: 10.1097/NCC.0000000000000923.
    [44]
    BARRAULT-COUCHOURON M, MICHELI N, SOUBEYRAN P. Exploring determinants of interdisciplinary collaboration within a geriatric oncology setting: A mixed-method study[J]. Cancers, 2022, 14( 6): 1386. DOI: 10.3390/cancers14061386.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(2)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (50) PDF downloads(11) Cited by()
    Proportional views
    Related
        

    The first journal specializing in hepatobiliary and pancreatic diseases in China

    Supervisor：Ministry of Education of the People's Republic of China

    Sponsor：Jilin University

    Academic Support: Chinese Society of Hepatology，Chinese Medical Association

    Address: 461 Xinjiang Road, Changchun

    Submit：0431-88782044

    Peer review：0431-88783542

    Email：lcgdb@vip.163.com

    About Journal

    Submission Guideline

    Journal Online

    Hepatobiliary College

    Guidelines

    YesterdayIP[]YesterdayPV[]TodayIP[]TodayPV[]Online[]

    Website Design © 2020 Editorial Board of Journal of Clinical Hepatology 吉ICP备10000617号-1 Supported by: Beijing Renhe Information Technology Co. Ltd  

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return