AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO025240260
Submit to EJMO
Cite this article
7
Download
55
Views
Journal Browser
Volume | Year
Issue
Search
Forthcoming Issue
Current Issue
View All
News and Announcements
View All
REVIEW ARTICLE

Prospects of CD44 in hepatocellular carcinoma: An emerging biomarker and therapeutic target

Maomao Shu1 ,  Juan Qu2 ,  Shunli Luo3 ,  Tao Xiao3 ,  Ziye Xiang3 ,  Lingying Yan3 ,  Jiaxing Liu3 ,  Yujia Liu3 ,  Xingjun Lu3* ,  Xiaozhen Peng3*
Show Less
1 Department of Clinical Laboratory, The First Affiliated Hospital of Hunan University of Medicine, Huaihua, China
2 Medical Genetics Laboratory, Huaihua City Maternal and Child Health Care Hospital, Huaihua, China
3 College of Laboratory Medicine, Hunan University of Medicine, Huaihua, China
EJMO, 025240260 https://doi.org/10.36922/EJMO025240260
Received: 14 June 2025 | Revised: 31 July 2025 | Accepted: 19 August 2025 | Published online: 7 October 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Download PDF
XML
Cite
Abstract

CD44, a single-transmembrane glycoprotein with diverse functional roles, has emerged as a critical regulator of tumor behavior, particularly in hepatocellular carcinoma (HCC). Elevated CD44 expression in HCC correlates with aggressive disease progression, positioning it as a promising diagnostic and prognostic biomarker. At the molecular level, CD44 orchestrates key oncogenic processes, including enhanced cellular proliferation, accelerated cell cycle progression, and increased migratory capacity, thereby driving HCC pathogenesis. As therapeutic strategies for HCC become more aggressive, invasive interventions are associated with adverse clinical outcomes, highlighting the need for targeted approaches. This review comprehensively analyzes current literature on CD44, addressing its structural diversity, isoform-specific functions, and signaling mechanisms in HCC. Furthermore, we discuss its prognostic significance, role in therapeutic resistance, and potential as a molecular target. By synthesizing these findings, this work aims to provide novel insights into early detection, accurate diagnosis, and the development of precision therapies for HCC, ultimately improving clinical outcomes.

Keywords
CD44
Biomarker
Therapeutic target
Hepatocellular carcinoma
Funding
This research was funded by the National Natural Sciences Foundation of Hunan province (grant numbers: 2024JJ7337 and 2023JJ5043).
Conflict of interest
The authors declare no conflicts of interest.
References
  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394-424. doi: 10.3322/caac.21492

 

  1. London WT, Mcglynn KA. Liver Cancer: Cancer Epidemiology and Prevention. New York: Oxford University Press; 2006.

 

  1. Llovet JM, Zucman-Rossi J, Pikarsky E, et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2016,2:16018. doi: 10.1038/nrdp.2016.18

 

  1. Zheng X, Liu X, Lei Y, Wang G, Liu M. Glypican-3: A novel and promising target for the treatment of hepatocellular carcinoma. Front Oncol. 2022,12:824208. doi: 10.3389/fonc.2022.824208

 

  1. Vlashi E, Lagadec C, Vergnes L, et al. Metabolic state of glioma stem cells and nontumorigenic cells. Proc Natl Acad Sci. 2011,108(38):16062-16067. doi: 10.1073/pnas.1106704108

 

  1. Gao W, Chen L, Ma Z, et al. Isolation and phenotypic characterization of colorectal cancer stem cells with organ-specific metastatic potential. Gastroenterology. 2013,145(3):636-646.e635. doi: 10.1053/j.gastro.2013.05.049

 

  1. Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997,3(7):730-737. doi: 10.1038/nm0797-730.

 

  1. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci. 2003,100(7):3983-3988. doi: 10.1073/pnas.0530291100.

 

  1. Kim CFB, Jackson EL, Woolfenden AE, et al. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell. 2005,121(6):823-835. doi: 10.1016/j.cell.2005.03.032.

 

  1. O’Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 2007,445(7123):106-110. doi: 10.1038/nature05372

 

  1. Yamashita T, Ji J, Budhu A, et al. EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features. Gastroenterology. 2009,136(3):1012-1024.e1014. doi: 10.1053/j.gastro.2008.12.004

 

  1. Ma S, Chan KW, Hu L, et al. Identification and characterization of tumorigenic liver cancer stem/progenitor cells. Gastroenterology. 2007,132(7):2542-2556. doi: 10.1053/j.gastro.2007.04.025

 

  1. Zhu Z, Hao X, Yan M, et al. Cancer stem/progenitor cells are highly enriched in CD133+CD44+ population in hepatocellular carcinoma. Int J Cancer. 2010,126(9):2067-2078. doi: 10.1002/ijc.24868

 

  1. Zöller M. CD44: Can a cancer-initiating cell profit from an abundantly expressed molecule? Nat Rev Cancer. 2011,11(4):254-267. doi: 10.1038/nrc3023

 

  1. Prochazka L, Tesarik R, Turanek J. Regulation of alternative splicing of CD44 in cancer. Cell Signal. 2014,26(10):2234-2239. doi: 10.1016/j.cellsig.2014.07.011

 

  1. Yan Y, Zuo X, Wei D. Concise review: Emerging role of CD44 in cancer stem cells: A promising biomarker and therapeutic target. Stem Cells Transl Med. 2015,4(9):1033-1043. doi: 10.5966/sctm.2015-0048

 

  1. Ishimoto T, Nagano O, Yae T, et al. CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc(-) and thereby promotes tumor growth. Cancer Cell. 2011,19(3):387-400. doi: 10.1016/j.ccr.2011.01.038

 

  1. Ponta H, Sherman L, Herrlich PA. CD44: From adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol. 2003,4(1):33-45. doi: 10.1038/nrm1004

 

  1. Brown RL, Reinke LM, Damerow MS, et al. CD44 splice isoform switching in human and mouse epithelium is essential for epithelial-mesenchymal transition and breast cancer progression. J Clin Invest. 2011,121(3):1064-1074. doi: 10.1172/jci44540

 

  1. Dang H, Steinway SN, Ding W, Rountree CB. Induction of tumor initiation is dependent on CD44s in c-Met+ hepatocellular carcinoma. BMC Cancer. 2015,15(1):161. doi: 10.1186/s12885-015-1166-4

 

  1. Gronthos S, Franklin DM, Leddy HA, Robey PG, Storms RW, Gimble JM. Surface protein characterization of human adipose tissue-derived stromal cells. J Cell Physiol. 2001,189(1):54-63. doi: 10.1002/jcp.1138

 

  1. Domev H, Amit M, Laevsky I, Dar A, Itskovitz-Eldor J. Efficient engineering of vascularized ectopic bone from human embryonic stem cell-derived mesenchymal stem cells. Tissue Eng Part A. 2012,18(21-22):2290-2302. doi: 10.1089/ten.TEA.2011.0371

 

  1. Banerjee S, Modi S, McGinn O, et al. Impaired synthesis of stromal components in response to minnelide improves vascular function, drug delivery, and survival in pancreatic cancer. Clin Cancer Res. 2016,22(2):415-425. doi: 10.1158/1078-0432.Ccr-15-1155

 

  1. Li L, Hao X, Qin J, et al. Antibody against CD44s inhibits pancreatic tumor initiation and postradiation recurrence in mice. Gastroenterology. 2014,146(4):1108-1118. doi: 10.1053/j.gastro.2013.12.035

 

  1. Matzke-Ogi A, Jannasch K, Shatirishvili M, et al. Inhibition of tumor growth and metastasis in pancreatic cancer models by interference with CD44v6 signaling. Gastroenterology. 2016,150(2):513-525.e10. doi: 10.1053/j.gastro.2015.10.020

 

  1. Todaro M, Gaggianesi M, Catalano V, et al. CD44v6 is a marker of constitutive and reprogrammed cancer stem cells driving colon cancer metastasis. Cell Stem Cell. 2014,14(3):342-356. doi: 10.1016/j.stem.2014.01.009

 

  1. Orian-Rousseau V. CD44 acts as a signaling platform controlling tumor progression and metastasis. Front Immunol. 2015,6:154. doi: 10.3389/fimmu.2015.00154

 

  1. Morrison H, Sherman LS, Legg J, et al. The NF2 tumor suppressor gene product, merlin, mediates contact inhibition of growth through interactions with CD44. Genes Dev. 2001,15(8):968-980. doi: 10.1101/gad.189601

 

  1. Orian-Rousseau V, Chen L, Sleeman JP, Herrlich P, Ponta H. CD44 is required for two consecutive steps in HGF/c-Met signaling. Genes Dev. 2002,16(23):3074-3086. doi: 10.1101/gad.242602

 

  1. Matzke A, Herrlich P, Ponta H, Orian-Rousseau V. A five-amino-acid peptide blocks Met- and Ron-dependent cell migration. Cancer Res. 2005,65(14):6105-6110. doi: 10.1158/0008-5472.Can-05-0207

 

  1. Lammich S, Okochi M, Takeda M, et al. Presenilin-dependent intramembrane proteolysis of CD44 leads to the liberation of its intracellular domain and the secretion of an Abeta-like peptide. J Biol Chem. 2002,277(47):44754-44759. doi: 10.1074/jbc.M206872200

 

  1. Chen C, Zhao S, Karnad A, Freeman JW. The biology and role of CD44 in cancer progression: Therapeutic implications. J Hematol Oncol. 2018,11(1):64. doi: 10.1186/s13045-018-0605-5

 

  1. Loh TJ, Moon H, Cho S, et al. CD44 alternative splicing and hnRNP A1 expression are associated with the metastasis of breast cancer. Oncol Rep. 2015,34(3):1231-1238. doi: 10.3892/or.2015.4110

 

  1. Mishra MN, Chandavarkar V, Sharma R, Bhargava D. Structure, function and role of CD44 in neoplasia. J Oral Maxillofac Pathol. 2019,23(2):267-272. doi: 10.4103/jomfp.JOMFP_246_18

 

  1. Liu X, Taftaf R, Kawaguchi M, et al. Homophilic CD44 interactions mediate tumor cell aggregation and polyclonal metastasis in patient-derived breast cancer models. Cancer Discov. 2019,9(1):96-113. doi: 10.1158/2159-8290.Cd-18-0065

 

  1. Wolf KJ, Shukla P, Springer K, et al. A mode of cell adhesion and migration facilitated by CD44-dependent microtentacles. Proc Natl Acad Sci U S A. 2020,117(21):11432-11443. doi: 10.1073/pnas.1914294117

 

  1. Hassn Mesrati M, Behrooz AB, Abuhamad AY, Syahir A. Understanding glioblastoma biomarkers: Knocking a mountain with a hammer. Cells. 2020,9(5):1236. doi: 10.3390/cells9051236

 

  1. Wang Z, Tang Y, Xie L, et al. The prognostic and clinical value of CD44 in colorectal cancer: A meta-analysis. Front Oncol. 2019,9:309. doi: 10.3389/fonc.2019.00309

 

  1. Li W, Qian L, Lin J, et al. CD44 regulates prostate cancer proliferation, invasion and migration via PDK1 and PFKFB4. Oncotarget. 2017,8(39):65143-65151. doi: 10.18632/oncotarget.17821

 

  1. Ludwig N, Szczepanski MJ, Gluszko A, et al. CD44(+) tumor cells promote early angiogenesis in head and neck squamous cell carcinoma. Cancer Lett. 2019,467:85-95. doi: 10.1016/j.canlet.2019.10.010

 

  1. Gzil A, Zarębska I, Bursiewicz W, Antosik P, Grzanka D, Szylberg Ł. Markers of pancreatic cancer stem cells and their clinical and therapeutic implications. Mol Biol Rep. 2019,46(6):6629-6645. doi: 10.1007/s11033-019-05058-1

 

  1. Durko L, Wlodarski W, Stasikowska-Kanicka O, et al. Expression and clinical significance of cancer stem cell markers CD24, CD44, and CD133 in pancreatic ductal adenocarcinoma and chronic pancreatitis. Dis Markers. 2017,2017:3276806. doi: 10.1155/2017/3276806

 

  1. Chen KL, Li D, Lu TX, Chang SW. Structural characterization of the CD44 stem region for standard and cancer-associated isoforms. Int J Mol Sci. 2020,21(1):336. doi: 10.3390/ijms21010336

 

  1. Bennett KL, Jackson DG, Simon JC, et al. CD44 isoforms containing exon V3 are responsible for the presentation of heparin-binding growth factor. J Cell Biol. 1995,128(4):687-698. doi: 10.1083/jcb.128.4.687

 

  1. Greenfield B, Wang WC, Marquardt H, et al. Characterization of the heparan sulfate and chondroitin sulfate assembly sites in CD44. J Biol Chem. 1999,274(4):2511-2517. doi: 10.1074/jbc.274.4.2511

 

  1. Hassn Mesrati M, Syafruddin SE, Mohtar MA, Syahir A. CD44: A multifunctional mediator of cancer progression. Biomolecules. 2021,11(12):1850. doi: 10.3390/biom11121850

 

  1. Jin L, Hope KJ, Zhai Q, Smadja-Joffe F, Dick JE. Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat Med. 2006,12(10):1167-1174. doi: 10.1038/nm1483

 

  1. Leung EL, Fiscus RR, Tung JW, et al. Non-small cell lung cancer cells expressing CD44 are enriched for stem cell-like properties. PLoS One. 2010,5(11):e14062. doi: 10.1371/journal.pone.0014062

 

  1. Haraguchi N, Ohkuma M, Sakashita H, et al. CD133+CD44+ population efficiently enriches colon cancer initiating cells. Ann Surg Oncol. 2008,15(10):2927-2933. doi: 10.1245/s10434-008-0074-0

 

  1. Lingala S, Cui YY, Chen X, et al. Immunohistochemical staining of cancer stem cell markers in hepatocellular carcinoma. Exp Mol Pathol. 2010,89(1):27-35. doi: 10.1016/j.yexmp.2010.05.005

 

  1. Yang ZF, Ho DW, Ng MN, et al. Significance of CD90+ cancer stem cells in human liver cancer. Cancer Cell. 2008,13(2):153-166. doi: 10.1016/j.ccr.2008.01.013

 

  1. Luo Y, Tan Y. Prognostic value of CD44 expression in patients with hepatocellular carcinoma: meta-analysis. Cancer Cell Int. 2016,16:47. doi: 10.1186/s12935-016-0325-2

 

  1. Liu R, Shen Y, Nan K, et al. Association between expression of cancer stem cell markers and poor differentiation of hepatocellular carcinoma: A meta-analysis (PRISMA). Medicine (Baltimore). 2015,94(31):e1306. doi: 10.1097/MD.0000000000001306

 

  1. Zhao Q, Zhou H, Liu Q, et al. Prognostic value of the expression of cancer stem cell-related markers CD133 and CD44 in hepatocellular carcinoma: From patients to patient-derived tumor xenograft models. Oncotarget. 2016,7(30):47431-47443. doi: 10.18632/oncotarget.10164

 

  1. Endo K, Terada T. Protein expression of CD44 (standard and variant isoforms) in hepatocellular carcinoma: Relationships with tumor grade, clinicopathologic parameters, p53 expression, and patient survival. J Hepatol. 2000,32(1):78-84. doi: 10.1016/s0168-8278(00)80192-0

 

  1. Kakehashi A, Ishii N, Sugihara E, Gi M, Saya H, Wanibuchi H. CD44 variant 9 is a potential biomarker of tumor initiating cells predicting survival outcome in hepatitis C virus-positive patients with resected hepatocellular carcinoma. Cancer Sci. 2016,107(5):609-618. doi: 10.1111/cas.12908

 

  1. Tovuu LO, Imura S, Utsunomiya T, et al. Role of CD44 expression in non-tumor tissue on intrahepatic recurrence of hepatocellular carcinoma. Int J Clin Oncol. 2013,18(4):651-656. doi: 10.1007/s10147-012-0432-6

 

  1. Naor D, Nedvetzki S, Golan I, Melnik L, Faitelson Y. CD44 in cancer. Crit Rev Clin Lab Sci. 2002,39(6):527-579. doi: 10.1080/10408360290795574

 

  1. Yang ZF, Ngai P, Ho DW, et al. Identification of local and circulating cancer stem cells in human liver cancer. Hepatology. 2008,47(3):919-928. doi: 10.1002/hep.22082

 

  1. Fujita N, Yaegashi N, Ide Y, et al. Expression of CD44 in normal human versus tumor endometrial tissues: Possible implication of reduced expression of CD44 in lymph-vascular space involvement of cancer cells. Cancer Res. 1994,54(14):3922-3928.

 

  1. He Y, Xue C, Yu Y, et al. CD44 is overexpressed and correlated with tumor progression in gallbladder cancer. Cancer Manag Res. 2018,10:3857-3865. doi: 10.2147/cmar.S175681

 

  1. Xie Z, Choong PF, Poon LF, et al. Inhibition of CD44 expression in hepatocellular carcinoma cells enhances apoptosis, chemosensitivity, and reduces tumorigenesis and invasion. Cancer Chemother Pharmacol. 2008,62(6):949-957. doi: 10.1007/s00280-008-0684-z

 

  1. Kim J, Jiang J, Badawi M, Schmittgen TD. miR-221 regulates CD44 in hepatocellular carcinoma through the PI3K-AKT-mTOR pathway. Biochem Biophys Res Commun. 2017,487(3):709-715. doi: 10.1016/j.bbrc.2017.04.121

 

  1. Li J, Ren H, Wang J, Zhang P, Shi X. Extracellular HMGB1 promotes CD44 expression in hepatocellular carcinoma via regulating miR-21. Aging (Albany NY). 2021,13(6):8380-8395. doi: 10.18632/aging.202649

 

  1. Wang Q, Lau WY, Zhang B, et al. Preoperative total cholesterol predicts postoperative outcomes after partial hepatectomy in patients with chronic hepatitis B- or C-related hepatocellular carcinoma. Surgery. 2014,155(2):263-270. doi: 10.1016/j.surg.2013.08.017

 

  1. Lee YL, Li WC, Tsai TH, Chiang HY, Ting CT. Body mass index and cholesterol level predict surgical outcome in patients with hepatocellular carcinoma in Taiwan - a cohort study. Oncotarget. 2016,7(16):22948-22959. doi: 10.18632/oncotarget.8312

 

  1. Yue S, Li J, Lee SY, et al. Cholesteryl ester accumulation induced by PTEN loss and PI3K/AKT activation underlies human prostate cancer aggressiveness. Cell Metab. 2014,19(3):393-406. doi: 10.1016/j.cmet.2014.01.019

 

  1. Lee SS, Li J, Tai JN, Ratliff TL, Park K, Cheng JX. Avasimibe encapsulated in human serum albumin blocks cholesterol esterification for selective cancer treatment. ACS Nano. 2015,9(3):2420-2432. doi: 10.1021/nn504025a

 

  1. Nicolson GL. Cell membrane fluid-mosaic structure and cancer metastasis. Cancer Res. 2015,75(7):1169-1176. doi: 10.1158/0008-5472.Can-14-3216

 

  1. Yang Z, Qin W, Chen Y, et al. Cholesterol inhibits hepatocellular carcinoma invasion and metastasis by promoting CD44 localization in lipid rafts. Cancer Lett. 2018,429:66-77. doi: 10.1016/j.canlet.2018.04.038

 

  1. Rani B, Malfettone A, Dituri F, et al. Galunisertib suppresses the staminal phenotype in hepatocellular carcinoma by modulating CD44 expression. Cell Death Dis. 2018,9(3):373. doi: 10.1038/s41419-018-0384-5

 

  1. Zhang J, He X, Wan Y, et al. CD44 promotes hepatocellular carcinoma progression via upregulation of YAP. Exp Hematol Oncol. 2021,10(1):54. doi: 10.1186/s40164-021-00247-w

 

  1. Hong W, Guan KL. The YAP and TAZ transcription co-activators: Key downstream effectors of the mammalian Hippo pathway. Semin Cell Dev Biol. 2012,23(7):785-793. doi: 10.1016/j.semcdb.2012.05.004

 

  1. Shin E, Kim J. The potential role of YAP in head and neck squamous cell carcinoma. Exp Mol Med. 2020,52(8):1264-1274. doi: 10.1038/s12276-020-00492-9

 

  1. Fan Z, Xia H, Xu H, et al. Standard CD44 modulates YAP1 through a positive feedback loop in hepatocellular carcinoma. Biomed Pharmacother. 2018,103:147-156. doi: 10.1016/j.biopha.2018.03.042

 

  1. Li J, Zhang Y, Ruan R, He W, Qian Y. The novel interplay between CD44 standard isoform and the caspase-1/IL1B pathway to induce hepatocellular carcinoma progression. Cell Death Dis. 2020,11(11):961. doi: 10.1038/s41419-020-03158-6

 

  1. Asai R, Tsuchiya H, Amisaki M, et al. CD44 standard isoform is involved in maintenance of cancer stem cells of a hepatocellular carcinoma cell line. Cancer Med. 2019,8(2):773-782. doi: 10.1002/cam4.1968

 

  1. Arabi L, Badiee A, Mosaffa F, Jaafari MR. Targeting CD44 expressing cancer cells with anti-CD44 monoclonal antibody improves cellular uptake and antitumor efficacy of liposomal doxorubicin. J Control Release. 2015, 220(Pt A):275-286. doi: 10.1016/j.jconrel.2015.10.044

 

  1. Zhang S, Wu CCN, Fecteau JF, et al. Targeting chronic lymphocytic leukemia cells with a humanized monoclonal antibody specific for CD44. Proc Natl Acad Sci U S A. 2013,110(15):6127-6132. doi: 10.1073/pnas.1221841110

 

  1. Maisel D, Birzele F, Voss E, et al. Targeting tumor cells with anti-CD44 antibody triggers macrophage-mediated immune modulatory effects in a cancer Xenograft model. PLoS One. 2016,11(7):e0159716. doi: 10.1371/journal.pone.0159716

 

  1. Chen X, Nagai Y, Zhu Z, et al. A spliced form of CD44 expresses the unique glycan that is recognized by the prostate cancer specific antibody F77. Oncotarget. 2018,9(3):3631-3640. doi: 10.18632/oncotarget.23341

 

  1. Qian H, Xia L, Ling P, Waxman S, Jing Y. CD44 ligation with A3D8 antibody induces apoptosis in acute myeloid leukemia cells through binding to CD44s and clustering lipid rafts. Cancer Biol Ther. 2012,13(13):1276-1283. doi: 10.4161/cbt.21784

 

  1. Khayrani AC, Mahmud H, Oo AKK, et al. Targeting ovarian cancer cells overexpressing CD44 with immunoliposomes encapsulating glycosylated paclitaxel. Int J Mol Sci. 2019,20(5):1042. doi: 10.3390/ijms20051042

 

  1. Lee S, Xie J, Chen X. Peptides and peptide hormones for molecular imaging and disease diagnosis. Chem Rev. 2010,110(5):3087.

 

  1. Zhang P, Cui Y, Anderson CF, et al. Peptide-based nanoprobes for molecular imaging and disease diagnostics. Chem Soc Rev. 2018,47(10):3490-3529. doi: 10.1039/c7cs00793k

 

  1. Wang W, Hu Z. Targeting peptide-based probes for molecular imaging and diagnosis. Adv Mater. 2019,31(45):e1804827. doi: 10.1002/adma.201804827

 

  1. Feng S, Meng X, Li Z, et al. Multi-modal imaging probe for glypican-3 overexpressed in orthotopic hepatocellular carcinoma. J Med Chem. 2021,64(21):15639-15650. doi: 10.1021/acs.jmedchem.1c00697

 

  1. Lo A, Lin CT, Wu HC. Hepatocellular carcinoma cell-specific peptide ligand for targeted drug delivery. Mol Cancer Ther. 2008,7(3):579-589. doi: 10.1158/1535-7163.Mct-07-2359

 

  1. Du B, Han H, Wang Z, et al. Targeted drug delivery to hepatocarcinoma in vivo by phage-displayed specific binding peptide. Mol Cancer Res. 2010,8(2):135-144. doi: 10.1158/1541-7786.Mcr-09-0339

 

  1. Juliano RL, Alam R, Dixit V, Kang HM. Cell-targeting and cell-penetrating peptides for delivery of therapeutic and imaging agents. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2009,1(3):324-335. doi: 10.1002/wnan.4

 

  1. de Serres M, Ellis B, Dillberger JE, et al. Immunogenicity of thrombopoietin mimetic peptide GW395058 in BALB/c mice and New Zealand white rabbits: Evaluation of the potential for thrombopoietin neutralizing antibody production in man. Stem Cells. 1999,17(4):203-209. doi: 10.1002/stem.170203

 

  1. Tangri S, Mothé BR, Eisenbraun J, et al. Rationally engineered therapeutic proteins with reduced immunogenicity. J Immunol. 2005,174(6):3187-3196. doi: 10.4049/jimmunol.174.6.3187

 

  1. Park HY, Lee KJ, Lee SJ, Yoon MY. Screening of peptides bound to breast cancer stem cell specific surface marker CD44 by phage display. Mol Biotechnol. 2012,51(3):212-220. doi: 10.1007/s12033-011-9458-7

 

  1. Cho JH, Lee SC, Ha NR, Lee SJ, Yoon MY. A novel peptide-based recognition probe for the sensitive detection of CD44 on breast cancer stem cells. Mol Cell Probes. 2015,29(6):492-499. doi: 10.1016/j.mcp.2015.05.014

 

  1. Taghipour-Sabzevar V, Sharifi T, Bagheri-Khoulenjani S, Goodarzi V, Moghaddam MM. Targeted delivery of a short antimicrobial peptide against CD44-overexpressing tumor cells using hyaluronic acid-coated chitosan nanoparticles: An in vitro study. J Nanopart Res 2020,22(5):1-16.

 

  1. Zhang X, Zhong Y, Miao Z, Yang Q. Hyaluronic acid promotes hepatocellular carcinoma proliferation by upregulating CD44 expression and enhancing glucose metabolism flux. Int Immunopharmacol. 2025,147:114035. doi: 10.1016/j.intimp.2025.114035

 

  1. Wu X, Meng X, Chang TS, et al. Multi-modal imaging for uptake of peptide ligand specific for CD44 by hepatocellular carcinoma. Photoacoustics. 2022,26:100355. doi: 10.1016/j.pacs.2022.100355

 

  1. Yang Y, Sun M, Li W, et al. Rebalancing TGF-β/Smad7 signaling via compound kushen injection in hepatic stellate cells protects against liver fibrosis and hepatocarcinogenesis. Clin Transl Med. 2021,11(7):e410. doi: 10.1002/ctm2.410

 

  1. Zhou Y, Lin F, Wan T, et al. ZEB1 enhances Warburg effect to facilitate tumorigenesis and metastasis of HCC by transcriptionally activating PFKM. Theranostics. 2021,11(12):5926-5938. doi: 10.7150/thno.56490

 

  1. Zong Z, Zou J, Mao R, et al. M1 macrophages induce PD-L1 expression in hepatocellular carcinoma cells through IL-1β signaling. Front Immunol. 2019,10:1643. doi: 10.3389/fimmu.2019.01643

 

  1. Anvarnia A, Mohaddes-Gharamaleki F, Asadi M, Akbari M, Yousefi B, Shanehbandi D. Dysregulated microRNAs in colorectal carcinogenesis: New insight to cell survival and apoptosis regulation. J Cell Physiol. 2019,234(12):21683-21693. doi: 10.1002/jcp.28872

 

  1. Tamjidifar R, Akbari M, Tarzi S, et al. Prognostic and diagnostic values of miR-506 and SPON 1 in colorectal cancer with clinicopathological considerations. J Gastrointest Cancer. 2021,52(1):125-129. doi: 10.1007/s12029-019-00356-0

 

  1. Xu J, Ji L, Liang Y, et al. CircRNA-SORE mediates sorafenib resistance in hepatocellular carcinoma by stabilizing YBX1. Signal Transduct Target Ther. 2020,5(1):298. doi: 10.1038/s41392-020-00375-5

 

  1. Yang XM, Wang XQ, Hu LP, et al. Nucleolar HEAT repeat containing 1 up-regulated by the mechanistic target of rapamycin complex 1 signaling promotes hepatocellular carcinoma growth by dominating ribosome biogenesis and proteome homeostasis. Gastroenterology. 2023,165(3):629-646. doi: 10.1053/j.gastro.2023.05.029

 

  1. Yu AM, Choi YH, Tu MJ. RNA drugs and RNA targets for small molecules: Principles, progress, and challenges. Pharmacol Rev. 2020,72(4):862-898. doi: 10.1124/pr.120.019554

 

  1. Smith ES, Whitty E, Yoo B, Moore A, Sempere LF, Medarova Z. Clinical applications of short non-coding RNA-based therapies in the era of precision medicine. Cancers (Basel). 2022,14(6):1588. doi: 10.3390/cancers14061588

 

  1. Traber GM, Yu AM. RNAi-based therapeutics and novel RNA bioengineering technologies. J Pharmacol Exp Ther. 2023,384(1):133-154. doi: 10.1124/jpet.122.001234

 

  1. Hu B, Ma Y, Yang Y, Zhang L, Han H, Chen J. CD44 promotes cell proliferation in non-small cell lung cancer. Oncol Lett. 2018;15:5627-5633. doi: 10.3892/ol.2018.8051

 

  1. Yin J, Zhang H, Wu X, et al. CD44 inhibition attenuates EGFR signaling and enhances cisplatin sensitivity in human EGFR wildtype nonsmallcell lung cancer cells. Int J Mol Med. 2020,45(6):1783-1792. doi: 10.3892/ijmm.2020.4562

 

  1. Yang X, Iyer AK, Singh A, et al. MDR1 siRNA loaded hyaluronic acid-based CD44 targeted nanoparticle systems circumvent paclitaxel resistance in ovarian cancer. Sci Rep. 2015,5:8509. doi: 10.1038/srep08509

 

  1. Tirella A, Kloc-Muniak K, Good L, et al. CD44 targeted delivery of siRNA by using HA-decorated nanotechnologies for KRAS silencing in cancer treatment. Int J Pharm. 2019,561:114-123. doi: 10.1016/j.ijpharm.2019.02.032

 

  1. Pothuraju R, Rachagani S, Krishn SR, et al. Molecular implications of MUC5AC-CD44 axis in colorectal cancer progression and chemoresistance. Mol Cancer. 2020,19(1):37. doi: 10.1186/s12943-020-01156-y

 

  1. Porcellini S, Asperti C, Corna S, et al. CAR T cells redirected to CD44v6 control tumor growth in lung and ovary adenocarcinoma bearing mice. Front Immunol. 2020,11:99. doi: 10.3389/fimmu.2020.00099

 

  1. Wang H, Ye X, Ju Y, et al. Minicircle DNA-mediated CAR T cells targeting CD44 suppressed hepatocellular carcinoma both in vitro and in vivo. Onco Targets Ther. 2020,13:3703-3716. doi: 10.2147/ott.S247836

 

  1. Alhabbab RY. Targeting cancer stem cells by genetically engineered chimeric antigen receptor T cells. Front Genet. 2020,11:312. doi: 10.3389/fgene.2020.00312

 

  1. Porter CE, Rosewell Shaw A, Jung Y, et al. Oncolytic adenovirus armed with BiTE, cytokine, and checkpoint inhibitor enables CAR T cells to control the growth of heterogeneous tumors. Mol Ther. 2020,28(5):1251-1262. doi: 10.1016/j.ymthe.2020.02.016

 

  1. Tu Y, Kim JS. Selective gene transfer to hepatocellular carcinoma using homing peptide-grafted cationic liposomes. J Microbiol Biotechnol. 2010,20(4):821-827.

 

  1. Liao D, Liu Z, Wrasidlo WJ, et al. Targeted therapeutic remodeling of the tumor microenvironment improves an HER-2 DNA vaccine and prevents recurrence in a murine breast cancer model. Cancer Res. 2011,71(17):5688-5696. doi: 10.1158/0008-5472.Can-11-1264

 

  1. Liao D, Liu Z, Wrasidlo W, et al. Synthetic enzyme inhibitor: A novel targeting ligand for nanotherapeutic drug delivery inhibiting tumor growth without systemic toxicity. Nanomedicine. 2011,7(6):665-673. doi: 10.1016/j.nano.2011.03.001

 

  1. Kim HS, Cho HR, Choi SH, Woo JS, Moon WK. In vivo imaging of tumor transduced with bimodal lentiviral vector encoding human ferritin and green fluorescent protein on a 1.5T clinical magnetic resonance scanner. Cancer Res. 2010,70(18):7315-7324. doi: 10.1158/0008-5472.Can-10-0241

 

  1. Akins EJ, Dubey P. Noninvasive imaging of cell-mediated therapy for treatment of cancer. J Nucl Med. 2008,49 Suppl 2(2):180S-195S. doi: 10.2967/jnumed.107.045971

 

  1. Shah K, Jacobs A, Breakefield XO, Weissleder R. Molecular imaging of gene therapy for cancer. Gene Ther. 2004,11(15):1175-1187. doi: 10.1038/sj.gt.3302278

 

  1. Nisha R, Kumar P, Kumar U, et al. Assessment of hyaluronic acid-modified imatinib mesylate cubosomes through CD44 targeted drug delivery in NDEA-induced hepatic carcinoma. Int J Pharm. 2022,622:121848. doi: 10.1016/j.ijpharm.2022.121848
Share
Back to top
Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here
Accept