<?xml version="1.1" encoding="utf-8"?>
<article xsi:noNamespaceSchemaLocation="http://jats.nlm.nih.gov/publishing/1.1/xsd/JATS-journalpublishing1-mathml3.xsd" dtd-version="1.1" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"><front><journal-meta><journal-id journal-id-type="publisher-id">PAR</journal-id><journal-title-group><journal-title>Proceedings of Anticancer Research</journal-title></journal-title-group><issn>2208-3545</issn><eissn>2208-3553</eissn><publisher><publisher-name>Bio-Byword Scientific Publishing Pty. Ltd.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.26689/par.v8i6.7957</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title>Exploring the Role of Liver Cancer Stem Cells in Hepatocellular Carcinoma Metastasis</title><url>https://artdesignp.com/journal/PAR/8/6/10.26689/par.v8i6.7957</url><author>FatimaMaria,RiazMaria,AmjadMuhammad,WaqasMuhammad,RazaMuhammad Hashim</author><pub-date pub-type="publication-year"><year>2024</year></pub-date><volume>8</volume><issue>6</issue><history><date date-type="pub"><published-time>2024-11-22</published-time></date></history><abstract>Metastasis refers to disseminating cancerous tumors from their primary site to distant locations inside the body. Cancer cells must go through a sequence of events called the “metastatic cascade” to develop metastases. Each stage necessitates a unique functional alteration. Cancer stem cells (CSCs) play a crucial role in tumor metastasis, but understanding their dynamic behavior and regulating mechanisms remains incomplete. This review explores the influence of liver CSCs on the biological processes that drive the spread and growth of cancer cells, as described by the “metastatic cascade” concept. Liver CSCs can spread to other organs by undergoing epithelial-mesenchymal transition (EMT). This alteration in the microenvironment facilitates cellular dissemination, immune surveillance evasion, dormancy induction, and subsequent reactivation. To effectively prevent and treat advanced hepatocellular carcinoma (HCC) metastases, it is crucial to understand the heterogeneity and features of liver CSCs involved in these processes.</abstract><keywords/></article-meta></front><body/><back><ref-list><ref id="B1" content-type="article"><label>1</label><element-citation publication-type="journal"><p>Choi S, Kim BK, Yon DK, et al., 2023, Global Burden of Primary Liver Cancer and its Association with Underlying Aetiologies, Sociodemographic Status, and Sex Differences from 1990–2019: A DALY-Based Analysis of the Global Burden of Disease 2019 Study. Hepatology, 29(2): 433.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B2" content-type="article"><label>2</label><element-citation publication-type="journal"><p>Ahn KS, Kang KJ, Hepatology M, 2019, Appropriate Treatment Modality for Solitary Small Hepatocellular Carcinoma: Radiofrequency Ablation vs. Resection vs. Transplantation? Journal of Clinical and Experimental Hepatology, 25(4): 354.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B3" content-type="article"><label>3</label><element-citation publication-type="journal"><p>Katai H, Ishikawa T, Akazawa K, et al., 2018, Five-Year Survival Analysis of Surgically Resected Gastric Cancer Cases in Japan: A Retrospective Analysis of More Than 100,000 Patients from the Nationwide Registry of the Japanese Gastric Cancer Association (2001–2007). Gastric Cancer, 21: 144–154.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B4" content-type="article"><label>4</label><element-citation publication-type="journal"><p>Waks AG, Winer EP, 2019, Breast Cancer Treatment: A Review. Journal of the American Medical Association, 321(3): 288–300.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B5" content-type="article"><label>5</label><element-citation publication-type="journal"><p>Das V, Bhattacharya S, Chikkaputtaiah C, et al., 2019, The Basics of Epithelial-Mesenchymal Transition (EMT): A Study from a Structure, Dynamics, and Functional Perspective. Journal of Cellular Physiology, 234(9): 14535–14555.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B6" content-type="article"><label>6</label><element-citation publication-type="journal"><p>Yousaf A, Tasneem N, Mustafa A, et al., 2021, Gastric Cancer Associated Risk Factors and Prevalence in Pakistan. Journal of Cancer Research and Therapeutics, 1(2): 73–78.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B7" content-type="article"><label>7</label><element-citation publication-type="journal"><p>Moon AM, Singal AG, Tapper EB, et al., 2020, Contemporary Epidemiology of Chronic Liver Disease and Cirrhosis. Clinical Gastroenterology and Hepatology, 18(12): 2650–2666.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B8" content-type="article"><label>8</label><element-citation publication-type="journal"><p>Asrani SK, Devarbhavi H, Eaton J, et al., 2019, Burden of Liver Diseases in the World. Journal of Hepatology, 70(1): 151–171.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B9" content-type="article"><label>9</label><element-citation publication-type="journal"><p>Durand F, Levitsky J, Cauchy F, et al., 2019, Age and Liver Transplantation. Journal of Hepatology, 70(4): 745–758.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B10" content-type="article"><label>10</label><element-citation publication-type="journal"><p>Liu R, Rizzo S, Whipple S, et al., 2021, Evaluating Eligibility Criteria of Oncology Trials Using Real-World Data and AI. Nature, 592(7855): 629–633.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B11" content-type="article"><label>11</label><element-citation publication-type="journal"><p>Maryam S, Rasheed M, Javed I, et al., 2021, Synthesis and Function of Multi-Modality Probe for Early Tumor Diagnosis in Mouse. Asian Journal of Medical Sciences, 152–162.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B12" content-type="article"><label>12</label><element-citation publication-type="journal"><p>Filgueira NA, 2019, Hepatocellular Carcinoma Recurrence After Liver Transplantation: Risk Factors, Screening and Clinical Presentation. World Journal of Hepatology, 11(3): 261.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B13" content-type="article"><label>13</label><element-citation publication-type="journal"><p>Mamone G, Caruso S, Milazzo M, et al., 2023, Imaging of Hepatocellular Carcinoma Recurrence After Liver Transplantation. Insights in Imaging, 14(1): 84.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B14" content-type="article"><label>14</label><element-citation publication-type="journal"><p>Chidambaranathan-Reghupaty S, Fisher PB, Sarkar D, 2021, Hepatocellular Carcinoma (HCC): Epidemiology, Etiology and Molecular Classification. Advances in Cancer Research, 149: 1–61.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B15" content-type="article"><label>15</label><element-citation publication-type="journal"><p>Lin YL, Li Y, 2020, Study on the Hepatocellular Carcinoma Model with Metastasis. Gastrointestinal Diseases, 7(3): 336–350.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B16" content-type="article"><label>16</label><element-citation publication-type="journal"><p>Dujon AM, Capp JP, Brown JS, et al., 2021, Is There One Key Step in the Metastatic Cascade? Cancer, 13(15): 3693.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B17" content-type="article"><label>17</label><element-citation publication-type="journal"><p>Popper H, 2020, Primary Tumor and Metastasis—Sectioning the Different Steps of the Metastatic Cascade. Translational Lung Cancer Research, 9(5): 2277.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B18" content-type="article"><label>18</label><element-citation publication-type="journal"><p>Sökeland G, Schumacher U, 2019, The Functional Role of Integrins During Intra- and Extravasation Within the Metastatic Cascade. Molecular Cancer, 18(1): 12.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B19" content-type="article"><label>19</label><element-citation publication-type="journal"><p>Chernosky NM, Tamagno I, 2021, The Role of the Innate Immune System in Cancer Dormancy and Relapse. Cancers, 13(22): 5621.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B20" content-type="article"><label>20</label><element-citation publication-type="journal"><p>Menzel L, Höpken UE, Rehm A, 2020, Angiogenesis in Lymph Nodes is a Critical Regulator of Immune Response and Lymphoma Growth. Frontiers in Immunology, 11: 591741.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B21" content-type="article"><label>21</label><element-citation publication-type="journal"><p>Fares J, Fares MY, Khachfe HH, et al., 2020, Molecular Principles of Metastasis: A Hallmark of Cancer Revisited. Signal Transduction and Therapy, 5(1): 28.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B22" content-type="article"><label>22</label><element-citation publication-type="journal"><p>Massague J, Ganesh K, 2021, Metastasis-Initiating Cells and Ecosystems. Cancer Discovery, 11(4): 971–994.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B23" content-type="article"><label>23</label><element-citation publication-type="journal"><p>Truman JW, 2019, The Evolution of Insect Metamorphosis. Current Biology, 29(23): R1252–R1268.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B24" content-type="article"><label>24</label><element-citation publication-type="journal"><p>Bergers G, Fendt SM, 2021, The Metabolism of Cancer Cells During Metastasis. Nature Reviews Cancer, 21(3): 162–180.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B25" content-type="article"><label>25</label><element-citation publication-type="journal"><p>Liang L, Kaufmann AM, 2023, The Significance of Cancer Stem Cells and Epithelial-Mesenchymal Transition in Metastasis and Anti-Cancer Therapy. International Journal of Molecular Sciences, 24(3): 2555.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B26" content-type="article"><label>26</label><element-citation publication-type="journal"><p>Aramini B, Masciale V, Arienti C, et al., 2022, Cancer Stem Cells (CSCs), Circulating Tumor Cells (CTCs) and Their Interplay with Cancer-Associated Fibroblasts (CAFs): A New World of Targets and Treatments. Cancers, 14(10): 2408.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B27" content-type="article"><label>27</label><element-citation publication-type="journal"><p>Lee TK-W, Guan X-Y, Ma S, 2022, Cancer Stem Cells in Hepatocellular Carcinoma—From Origin to Clinical Implications. Nature Reviews Gastroenterology and Hepatology, 19(1): 26–44.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B28" content-type="article"><label>28</label><element-citation publication-type="journal"><p>Qing X, Xu W, Zong J, et al., 2021, Emerging Treatment Modalities for Systemic Therapy in Hepatocellular Carcinoma. Biomedicine Research International, 9(1): 64.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B29" content-type="article"><label>29</label><element-citation publication-type="journal"><p>Ullah MW, Manan S, Khattak WA, et al., 2020, Biotemplate-Mediated Green Synthesis and Applications of Nanomaterials. Current Pharmaceutical Design, 26(45): 5819–5836.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B30" content-type="article"><label>30</label><element-citation publication-type="journal"><p>Lim JR, Mouawad J, Gorton OK, et al., 2021, Cancer Stem Cell Characteristics and Their Potential as Therapeutic Targets. Medical Oncology, 38(7): 76.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B31" content-type="article"><label>31</label><element-citation publication-type="journal"><p>Ho DWH, Tsui YM, Sze KMF, et al., 2019, Single-Cell Transcriptomics Reveals the Landscape of Intra-Tumoral Heterogeneity and Stemness-Related Subpopulations in Liver Cancer. Cell, 459: 176–185.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B32" content-type="article"><label>32</label><element-citation publication-type="journal"><p>Alqahtani A, Khan Z, Alloghbi A, et al., 2019, Hepatocellular Carcinoma: Molecular Mechanisms and Targeted Therapies. Medicine, 55(9): 526.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B33" content-type="article"><label>33</label><element-citation publication-type="journal"><p>Zarębska I, Gzil A, Durślewicz J, et al., 2021, The Clinical, Prognostic and Therapeutic Significance of Liver Cancer Stem Cells and Their Markers. Gastroenterology, 45(3): 101664.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B34" content-type="article"><label>34</label><element-citation publication-type="journal"><p>Ahn JC, Teng PC, Chen PJ, et al., 2021, Detection of Circulating Tumor Cells and Their Implications as a Biomarker for Diagnosis, Prognostication, and Therapeutic Monitoring in Hepatocellular Carcinoma. Hepatology, 73(1): 422–436.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B35" content-type="article"><label>35</label><element-citation publication-type="journal"><p>Ribatti D, Tamma R, Annese T, 2020, Epithelial-Mesenchymal Transition in Cancer: A Historical Overview. Translational Oncology, 13(6): 100773.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B36" content-type="article"><label>36</label><element-citation publication-type="journal"><p>Lv J, Chen FK, Liu C, et al., 2020, Zoledronic Acid Inhibits Thyroid Cancer Stemness and Metastasis by Repressing M2-Like Tumor-Associated Macrophages Induced Wnt/β-Catenin Pathway. Life Sciences, 256: 117925.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B37" content-type="article"><label>37</label><element-citation publication-type="journal"><p>Gaponova A, Rodin S, Mazina A, et al., 2020, Epithelial-Mesenchymal Transition: Role in Cancer Progression and the Perspectives of Antitumor Treatment. Advances in Nanoscience, 12(3(46)): 4–23.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B38" content-type="article"><label>38</label><element-citation publication-type="journal"><p>Papadaki MA, Stoupis G, Theodoropoulos PA, et al., 2019, Circulating Tumor Cells with Stemness and Epithelial-to-Mesenchymal Transition Features Are Chemoresistant and Predictive of Poor Outcome in Metastatic Breast Cancer. Molecular Cancer Therapeutics, 18(2): 437–447.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B39" content-type="article"><label>39</label><element-citation publication-type="journal"><p>Li B, Cao Y, Meng G, et al., 2019, Targeting Glutaminase 1 Attenuates Stemness Properties in Hepatocellular Carcinoma by Increasing Reactive Oxygen Species and Suppressing Wnt/β-Catenin Pathway. Experimental Cell Research, 39: 239–254.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B40" content-type="article"><label>40</label><element-citation publication-type="journal"><p>Devan AR, Pavithran K, Nair B, et al., 2022, Deciphering the Role of Transforming Growth Factor-Beta 1 as a Diagnostic-Prognostic-Therapeutic Candidate Against Hepatocellular Carcinoma. World Journal of Gastroenterology, 28(36): 5250.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B41" content-type="article"><label>41</label><element-citation publication-type="journal"><p>Imodoye SO, Adedokun KA, Muhammed AO, et al., 2021, Understanding the Complex Milieu of Epithelial-Mesenchymal Transition in Cancer Metastasis: New Insight into the Roles of Transcription Factors. Frontiers in Oncology, 11: 762817.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B42" content-type="article"><label>42</label><element-citation publication-type="journal"><p>Hajizadeh F, Okoye I, Esmaily M, et al., 2019, Hypoxia Inducible Factors in the Tumor Microenvironment as Therapeutic Targets of Cancer Stem Cells. Life Sciences, 237: 116952.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B43" content-type="article"><label>43</label><element-citation publication-type="journal"><p>Papadakos SP, Arvanitakis K, Stergiou IE, et al., 2023, The Role of TLR4 in the Immunotherapy of Hepatocellular Carcinoma: Can We Teach an Old Dog New Tricks? Cancers, 15(10): 2795.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B44" content-type="article"><label>44</label><element-citation publication-type="journal"><p>Tripathi S, Levine H, Jolly MK, 2020, The Physics of Cellular Decision Making During Epithelial-Mesenchymal Transition. Annual Review of Biophysics, 49: 1–18.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B45" content-type="article"><label>45</label><element-citation publication-type="journal"><p>Wan S, Kim TH, Smith KJ, et al., 2019, New Labyrinth Microfluidic Device Detects Circulating Tumor Cells Expressing Cancer Stem Cell Marker and Circulating Tumor Microemboli in Hepatocellular Carcinoma. Scientific Reports, 9(1): 18575.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B46" content-type="article"><label>46</label><element-citation publication-type="journal"><p>Roshan MK, Soltani A, Soleimani A, et al., 2019, Role of AKT and mTOR Signaling Pathways in the Induction of Epithelial-Mesenchymal Transition (EMT) Process. Biomedicine &amp; Pharmacotherapy, 165: 229–234.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B47" content-type="article"><label>47</label><element-citation publication-type="journal"><p>Orrapin S, Udomruk S, Lapisatepun W, et al., 2022, Clinical Implication of Circulating Tumor Cells Expressing Epithelial Mesenchymal Transition (EMT) and Cancer Stem Cell (CSC) Markers and Their Perspective in HCC: A Systematic Review. Cancers, 14(14): 3373.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B48" content-type="article"><label>48</label><element-citation publication-type="journal"><p>Wu Q, Zhou L, Lv D, et al., 2019, Exosome-Mediated Communication in the Tumor Microenvironment Contributes to Hepatocellular Carcinoma Development and Progression. Journal of Hepatology and Oncology, 12: 1–11.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B49" content-type="article"><label>49</label><element-citation publication-type="journal"><p>Chen C, Wang Z, Ding Y, et al., 2023, Tumor Microenvironment-Mediated Immune Evasion in Hepatocellular Carcinoma. Frontiers in Immunology, 14: 1133308.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B50" content-type="article"><label>50</label><element-citation publication-type="journal"><p>Walker C, Mojares E, del Río Hernández A, 2018, Role of Extracellular Matrix in Development and Cancer Progression. International Journal of Molecular Sciences, 19(10): 3028.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B51" content-type="article"><label>51</label><element-citation publication-type="journal"><p>Cirri P, Chiarugi P, 2012, Cancer-Associated-Fibroblasts and Tumour Cells: A Diabolic Liaison Driving Cancer Progression. Cancer &amp; Metabolism Reviews, 31: 195–208.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B52" content-type="article"><label>52</label><element-citation publication-type="journal"><p>Kuppa SS, Kim HK, Kang JY, et al., 2022, Role of Mesenchymal Stem Cells and Their Paracrine Mediators in Macrophage Polarization: An Approach to Reduce Inflammation in Osteoarthritis. International Journal of Molecular Sciences, 23(21): 13016.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B53" content-type="article"><label>53</label><element-citation publication-type="journal"><p>Fang X, Yan Q, Liu S, et al., 2022, Cancer Stem Cells in Hepatocellular Carcinoma: Intrinsic and Extrinsic Molecular Mechanisms in Stemness Regulation. International Journal of Molecular Sciences, 23(20): 12327.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B54" content-type="article"><label>54</label><element-citation publication-type="journal"><p>Mitra A, Yan J, Xia X, et al., 2017, IL6‐Mediated Inflammatory Loop Reprograms Normal to Epithelial‐Mesenchymal Transition+ Metastatic Cancer Stem Cells in Preneoplastic Liver of Transforming Growth Factor Beta–Deficient β2‐Spectrin+/− Mice. Hepatology, 65(4): 1222–1236.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B55" content-type="article"><label>55</label><element-citation publication-type="journal"><p>Ghotra VP, Puigvert JC, Danen EH, 2009, The Cancer Stem Cell Microenvironment and Anti-Cancer Therapy. International Journal of Radiation Biology, 85(11): 955–962.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B56" content-type="article"><label>56</label><element-citation publication-type="journal"><p>Najafi M, Farhood B, Mortezaee K, 2019, Cancer Stem Cells (CSCs) in Cancer Progression and Therapy. Journal of Cellular Physiology, 234(6): 8381–8395.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B57" content-type="article"><label>57</label><element-citation publication-type="journal"><p>Liu Y, Cao X, 2016, Characteristics and Significance of the Pre-Metastatic Niche. Cancer Cell, 30(5): 668–681.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B58" content-type="article"><label>58</label><element-citation publication-type="journal"><p>Wang D, Li Y, Ge H, et al., 2022, The Extracellular Matrix: A Key Accomplice of Cancer Stem Cell Migration, Metastasis Formation, and Drug Resistance in PDAC. Cancers, 14(16): 3998.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B59" content-type="article"><label>59</label><element-citation publication-type="journal"><p>Wilson GK, Tennant DA, McKeating JA, 2014, Hypoxia Inducible Factors in Liver Disease and Hepatocellular Carcinoma: Current Understanding and Future Directions. Journal of Hepatology, 61(6): 1397–1406.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B60" content-type="article"><label>60</label><element-citation publication-type="journal"><p>Tsui YM, Chan LK, Ng IOL, 2020, Cancer Stemness in Hepatocellular Carcinoma: Mechanisms and Translational Potential. British Journal of Cancer, 122(10): 1428–1440.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B61" content-type="article"><label>61</label><element-citation publication-type="journal"><p>Muz B, de la Puente P, Azab F, et al., 2015, The Role of Hypoxia in Cancer Progression, Angiogenesis, Metastasis, and Resistance to Therapy, Hematology, 83–92.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B62" content-type="article"><label>62</label><element-citation publication-type="journal"><p>Sultan H, 2021, Protein and Polysaccharide Base Biomaterial for the Formation of Composite Bone Scaffold, American Journal of Medical Sciences, 80–88.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B63" content-type="article"><label>63</label><element-citation publication-type="journal"><p>Sainz JB, Carron E, Vallespinós M, et al., 2016, Cancer Stem Cells and Macrophages: Implications in Tumor Biology and Therapeutic Strategies, Mediators of Inflammation, 2016(1): 9012369.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B64" content-type="article"><label>64</label><element-citation publication-type="journal"><p>Yamashita T, Wang XW, 2013, Cancer Stem Cells in the Development of Liver Cancer, The Journal of Clinical Investigation, 123(5): 1911–1918.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B65" content-type="article"><label>65</label><element-citation publication-type="journal"><p>Aman MN, 2023, The Role of Extracellular Matrix in Tumor Progression and Treatment Response.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B66" content-type="article"><label>66</label><element-citation publication-type="journal"><p>Wu Y, Zhang J, Zhang X, et al., 2020, Cancer Stem Cells: A Potential Breakthrough in HCC-Targeted Therapy, Frontiers in Pharmacology, 11: 198.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B67" content-type="article"><label>67</label><element-citation publication-type="journal"><p>Sajid T, Khan J, Abbas Z, et al., 2024, Targeting Cancers: Uncovering the Potential Roles of Potato Tissue Culture as Anti-Cancer Agents—A Secondary Publication, Proceedings of Annual Research, 8(3): 36–50.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B68" content-type="article"><label>68</label><element-citation publication-type="journal"><p>He X, Lee B, Jiang Y, 2022, Extracellular Matrix in Cancer Progression and Therapy, Medical Research, 2(2): 125–139.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B69" content-type="article"><label>69</label><element-citation publication-type="journal"><p>Riaz M, Zubair M, Iqbal MK, et al., 2024, Exploring the Platelet and Cancer Cell Interaction in Metastasis Targeting: Platelets and Cancer Cell Interaction, Journal of Clinical Oncology and Medical Sciences, 4(2): 834–844.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B70" content-type="article"><label>70</label><element-citation publication-type="journal"><p>Sleeboom JJ, van Tienderen GS, Schenke-Layland K, et al., 2024, The Extracellular Matrix as Hallmark of Cancer and Metastasis: From Biomechanics to Therapeutic Targets, Science Translational Medicine, 16(728): eadg3840.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B71" content-type="article"><label>71</label><element-citation publication-type="journal"><p>Tang ZY, Ye SL, Liu YK, et al., 2004, A Decade’s Studies on Metastasis of Hepatocellular Carcinoma, Chinese Journal of Oncology, 130: 187–196.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B72" content-type="article"><label>72</label><element-citation publication-type="journal"><p>Wang S, Chen L, Liu W, 2022, Matrix Stiffness-Dependent STEAP3 Coordinated with PD-L2 Identify Tumor Responding to Sorafenib Treatment in Hepatocellular Carcinoma, Cancer Cell International, 22(1): 318.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B73" content-type="article"><label>73</label><element-citation publication-type="journal"><p>Sun Y, Li H, Chen Q, et al., 2021, The Distribution of Liver Cancer Stem Cells Correlates with the Mechanical Heterogeneity of Liver Cancer Tissue, Hepatology and Cell Biology, 156: 47–58.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B74" content-type="article"><label>74</label><element-citation publication-type="journal"><p>Lam KH, Ma S, 2023, Noncellular Components in the Liver Cancer Stem Cell Niche: Biology and Potential Clinical Implications, Hepatology, 78(3): 991–1005.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B75" content-type="article"><label>75</label><element-citation publication-type="journal"><p>Lv D, Chen L, Du L, et al., 2021, Emerging Regulatory Mechanisms Involved in Liver Cancer Stem Cell Properties in Hepatocellular Carcinoma, Frontiers in Cell and Developmental Biology, 9: 691410.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B76" content-type="article"><label>76</label><element-citation publication-type="journal"><p>Pantel K, Speicher M, 2016, The Biology of Circulating Tumor Cells, Oncology, 35(10): 1216–1224.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B77" content-type="article"><label>77</label><element-citation publication-type="journal"><p>Lozar T, Gersak K, Cemazar M, et al., 2019, The Biology and Clinical Potential of Circulating Tumor Cells, Reproductive Oncology, 53(2): 131–147.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B78" content-type="article"><label>78</label><element-citation publication-type="journal"><p>Van Dalum G, Holland L, Terstappen LW, 2012, Metastasis and Circulating Tumor Cells, European Oncology, 23(3): 87.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B79" content-type="article"><label>79</label><element-citation publication-type="journal"><p>Niu Q, Ye S, Zhao L, et al., 2024, The Role of Liver Cancer Stem Cells in Hepatocellular Carcinoma Metastasis, Cancer Biology and Therapy, 25(1): 2321768.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B80" content-type="article"><label>80</label><element-citation publication-type="journal"><p>Zhang Y, Li J, Cao L, et al., 2012, Circulating Tumor Cells in Hepatocellular Carcinoma: Detection Techniques, Clinical Implications, and Future Perspectives, Paper Presented at the Seminars in Oncology.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B81" content-type="article"><label>81</label><element-citation publication-type="journal"><p>Espejo-Cruz ML, González-Rubio S, Zamora-Olaya J, et al., 2021, Circulating Tumor Cells in Hepatocellular Carcinoma: A Comprehensive Review and Critical Appraisal. International Journal of Molecular Sciences, 22(23): 13073.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B82" content-type="article"><label>82</label><element-citation publication-type="journal"><p>Sentoso JW, Putra A, Alif I, et al., 2024, Targeting Unique Features of Quiescent Cancer Stem Cells to Overcome Resistance and Recurrence in Cancer Therapy: A Review. Journal of Cancer International, 14(1): 18–31.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B83" content-type="article"><label>83</label><element-citation publication-type="journal"><p>Lei MML, Lee TKW, 2021, Cancer Stem Cells: Emerging Key Players in Immune Evasion of Cancers. Frontiers in Cell and Developmental Biology, 9: 692940.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B84" content-type="article"><label>84</label><element-citation publication-type="journal"><p>De Angelis ML, Francescangeli F, Zeuner A, 2019, Breast Cancer Stem Cells as Drivers of Tumor Chemoresistance, Dormancy and Relapse: New Challenges and Therapeutic Opportunities. Cancers, 11(10): 1569.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B85" content-type="article"><label>85</label><element-citation publication-type="journal"><p>Liu YC, Yeh CT, Lin KH, 2020, Cancer Stem Cell Functions in Hepatocellular Carcinoma and Comprehensive Therapeutic Strategies. Cancers, 9(6): 1331.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B86" content-type="article"><label>86</label><element-citation publication-type="journal"><p>Amini P, Moazamiyanfar R, Dakkali MS, et al., 2023, Resveratrol in Cancer Therapy: From Stimulation of Genomic Stability to Adjuvant Cancer Therapy: A Comprehensive Review. Current Topics in Medicinal Chemistry, 23(8): 629–648.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B87" content-type="article"><label>87</label><element-citation publication-type="journal"><p>Chen K, Zhang C, Ling S, et al., 2021, The Metabolic Flexibility of Quiescent CSC: Implications for Chemotherapy Resistance. Cellular and Molecular Life Sciences, 12(9): 835.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B88" content-type="article"><label>88</label><element-citation publication-type="journal"><p>Wu Y, Hao X, Wei H, et al., 2023, Blockade of T‐cell Receptor with Ig and ITIM Domains Elicits Potent Antitumor Immunity in Naturally Occurring HBV‐related HCC in Mice. Hepatology, 77(3): 965–981.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B89" content-type="article"><label>89</label><element-citation publication-type="journal"><p>Galassi C, Musella M, Manduca N, et al., 2021, The Immune Privilege of Cancer Stem Cells: A Key to Understanding Tumor Immune Escape and Therapy Failure. Cancers, 10(9): 2361.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B90" content-type="article"><label>90</label><element-citation publication-type="journal"><p>Sajid M, Liu L, Sun C, 2022, The Dynamic Role of NK Cells in Liver Cancers: Role in HCC and HBV Associated HCC and Its Therapeutic Implications. Frontiers in Immunology, 13: 887186.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B91" content-type="article"><label>91</label><element-citation publication-type="journal"><p>Yang J, Antin P, Berx G, et al., 2020, Guidelines and Definitions for Research on Epithelial–Mesenchymal Transition. Nature Reviews Molecular Cell Biology, 21(6): 341–352.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B92" content-type="article"><label>92</label><element-citation publication-type="journal"><p>Majumder S, McGeachy MJ, 2021, IL-17 in the Pathogenesis of Disease: Good Intentions Gone Awry. Annual Review of Immunology, 39: 537–556.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B93" content-type="article"><label>93</label><element-citation publication-type="journal"><p>Shevyrev D, Tereshchenko V, 2020, Treg Heterogeneity, Function, and Homeostasis. Frontiers in Immunology, 10: 495736.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B94" content-type="article"><label>94</label><element-citation publication-type="journal"><p>Faubert B, Solmonson A, DeBerardinis RJ, 2020, Metabolic Reprogramming and Cancer Progression. Science, 368(6487): eaaw5473.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B95" content-type="article"><label>95</label><element-citation publication-type="journal"><p>Ahmed N, Escalona R, Leung D, et al., 2018, Tumour Microenvironment and Metabolic Plasticity in Cancer and Cancer Stem Cells: Perspectives on Metabolic and Immune Regulatory Signatures in Chemoresistant Ovarian Cancer Stem Cells. Seminars in Cancer Biology, 53: 265–281.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B96" content-type="article"><label>96</label><element-citation publication-type="journal"><p>Gottlieb RA, Bernstein D, 2016, Mitochondrial Remodeling: Rearranging, Recycling, and Reprogramming. Cancer Cell, 60(2): 88–101.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B97" content-type="article"><label>97</label><element-citation publication-type="journal"><p>Chang CW, Lo JF, Wang XW, 2019, Roles of Mitochondria in Liver Cancer Stem Cells. Development, 107: 35–41.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B98" content-type="article"><label>98</label><element-citation publication-type="journal"><p>Liu J, Qin X, Pan D, et al., 2019, Amino Acid‐Mediated Metabolism: A New Power to Influence Properties of Stem Cells. Stem Cells International, 2019(1): 6919463.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B99" content-type="article"><label>99</label><element-citation publication-type="journal"><p>Daniel Y, Lelou E, Aninat C, et al., 2021, Interplay Between Metabolism Reprogramming and Epithelial-to-Mesenchymal Transition in Cancer Stem Cells. Cancers, 13(8): 1973.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B100" content-type="article"><label>100</label><element-citation publication-type="journal"><p>Zubair M, Sultan HM, ur Rahman B, et al., 2024, CRISPR-Cas9: A Promising Therapeutic Approach for Diabetes Mellitus. International Journal of General Practice and Nutrition, 2(2): 43–56.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B101" content-type="article"><label>101</label><element-citation publication-type="journal"><p>Zhang Q, Li W, 2022, Correlation between Amino Acid Metabolism and Self-Renewal of Cancer Stem Cells: Perspectives in Cancer Therapy. World Journal of Stem Cells, 14(4): 267.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B102" content-type="article"><label>102</label><element-citation publication-type="journal"><p>Jain RK, 2012, Delivery of Molecular and Cellular Medicine to Solid Tumors. Advanced Drug Delivery Reviews, 64: 353–365.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B103" content-type="article"><label>103</label><element-citation publication-type="journal"><p>Hassan G, Seno M, 2020, Blood and Cancer: Cancer Stem Cells as Origin of Hematopoietic Cells in Solid Tumor Microenvironments. Cancer, 9(5): 1293.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B104" content-type="article"><label>104</label><element-citation publication-type="journal"><p>Nowicki A, Kulus M, Wieczorkiewicz M, et al., 2021, Ovarian Cancer and Cancer Stem Cells—Cellular and Molecular Characteristics, Signaling Pathways, and Usefulness as a Diagnostic Tool in Medicine and Oncology. Cancers, 13(16): 4178.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B105" content-type="article"><label>105</label><element-citation publication-type="journal"><p>Moore G, Annett S, McClements L, et al., 2020, Top Notch Targeting Strategies in Cancer: A Detailed Overview of Recent Insights and Current Perspectives. Cancers, 9(6): 1503.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B106" content-type="article"><label>106</label><element-citation publication-type="journal"><p>Yang L, Shi P, Zhao G, et al., 2020, Targeting Cancer Stem Cell Pathways for Cancer Therapy. Therapy, 5(1): 8.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B107" content-type="article"><label>107</label><element-citation publication-type="journal"><p>Becker AP, Sells BE, Haque SJ, et al., 2021, Tumor Heterogeneity in Glioblastomas: From Light Microscopy to Molecular Pathology. Cancers, 13(4): 761.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B108" content-type="article"><label>108</label><element-citation publication-type="journal"><p>Dong C, Ma H, Mi N, et al., 2024, Integrated Analysis of scRNA-seq and Bulk RNA-seq Reveals That GPRC5A is an Important Prognostic Gene in Pancreatic Cancer and is Associated with B-Cell Infiltration in Pancreatic Cancer. Frontiers in Oncology, 14: 1283164.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B109" content-type="article"><label>109</label><element-citation publication-type="journal"><p>Litvina E, Adams A, Barth A, et al., 2019, BRAIN Initiative: Cutting-Edge Tools and Resources for the Community. Journal of Neuroscience, 39(42): 8275–8284.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B110" content-type="article"><label>110</label><element-citation publication-type="journal"><p>Januškevičienė I, Petrikaitė V, 2019, Heterogeneity of Breast Cancer: The Importance of Interaction Between Different Tumor Cell Populations. Life Sciences, 239: 117009.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B111" content-type="article"><label>111</label><element-citation publication-type="journal"><p>Saviano A, Henderson NC, Baumert TF, 2020, Single-Cell Genomics and Spatial Transcriptomics: Discovery of Novel Cell States and Cellular Interactions in Liver Physiology and Disease Biology. Journal of Hepatology, 73(5): 1219–1230.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B112" content-type="article"><label>112</label><element-citation publication-type="journal"><p>Lehmann R, Lee CM, Shugart EC, et al., 2019, Human Organoids: A New Dimension in Cell Biology. Molecular Biology of the Cell, 30(10): 1129–1137.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B113" content-type="article"><label>113</label><element-citation publication-type="journal"><p>Ingber DE, 2022, Human Organs-on-Chips for Disease Modelling, Drug Development and Personalized Medicine. Nature Reviews Genetics, 23(8): 467–491.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B114" content-type="article"><label>114</label><element-citation publication-type="journal"><p>Wood LD, Ewald AJ, 2021, Organoids in Cancer Research: A Review for Pathologist‐Scientists. The Journal of Pathology, 254(4): 395–404.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B115" content-type="article"><label>115</label><element-citation publication-type="journal"><p>Neophytou CM, Panagi M, Stylianopoulos T, et al., 2021, The Role of Tumor Microenvironment in Cancer Metastasis: Molecular Mechanisms and Therapeutic Opportunities. Cancers, 13(9): 2053.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B116" content-type="article"><label>116</label><element-citation publication-type="journal"><p>Bocci F, Gearhart-Serna L, Boareto M, et al., 2019, Toward Understanding Cancer Stem Cell Heterogeneity in the Tumor Microenvironment. Proceedings of the National Academy of Sciences, 116(1): 148–157.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B117" content-type="article"><label>117</label><element-citation publication-type="journal"><p>Ahmed HMM, Nimmagadda SC, Al‐Matary YS, et al., 2022, Dexamethasone‐Mediated Inhibition of Notch Signalling Blocks the Interaction of Leukaemia and Mesenchymal Stromal Cells. British Journal of Haematology, 196(4): 995–1006.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B118" content-type="article"><label>118</label><element-citation publication-type="journal"><p>Zhu X, Zhang B, He Y, et al., 2021, Liver Organoids: Formation Strategies and Biomedical Applications. Trends in Endocrinology and Metabolism, 18(4): 573–585.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B119" content-type="article"><label>119</label><element-citation publication-type="journal"><p>Natale A, Vanmol K, Arslan A, et al., 2019, Technological Advancements for the Development of Stem Cell-Based Models for Hepatotoxicity Testing. Archives of Toxicology, 93: 1789–1805.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B120" content-type="article"><label>120</label><element-citation publication-type="journal"><p>Nimmakayala RK, Batra SK, Ponnusamy MP, 2019, Unraveling the Journey of Cancer Stem Cells from Origin to Metastasis. Biochimica et Biophysica Acta - Reviews on Cancer, 1871(1): 50–63.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B121" content-type="article"><label>121</label><element-citation publication-type="journal"><p>Nussinov R, Tsai CJ, Jang H, 2021, Anticancer Drug Resistance: An Update and Perspective. Drug Resistance Updates, 59: 100796.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B122" content-type="article"><label>122</label><element-citation publication-type="journal"><p>Wang R, Li J, Zhou X, et al., 2022, Single-Cell Genomic and Transcriptomic Landscapes of Primary and Metastatic Colorectal Cancer Tumors. Genomic Medicine, 14(1): 93.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B123" content-type="article"><label>123</label><element-citation publication-type="journal"><p>Chowdhury S, Hofree M, Lin K, et al., 2021, Implications of Intratumor Heterogeneity on Consensus Molecular Subtype (CMS) in Colorectal Cancer. Cancers, 13(19): 4923.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B124" content-type="article"><label>124</label><element-citation publication-type="journal"><p>Wang Y, Leaker B, Qiao G, et al., 2023, Precision-Cut Liver Slices as an Ex Vivo Model to Evaluate Antifibrotic Therapies for Liver Fibrosis and Cirrhosis. Biology, 8(11): e0558.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B125" content-type="article"><label>125</label><element-citation publication-type="journal"><p>Pearen MA, Lim HK, Gratte FD, et al., 2020, Murine Precision-Cut Liver Slices as an Ex Vivo Model of Liver Biology. Journal, (157): e60992.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B126" content-type="article"><label>126</label><element-citation publication-type="journal"><p>Zakrzewski W, Dobrzyński M, Szymonowicz M, et al., 2019, Stem Cells: Past, Present, and Future. Stem Cell Research &amp; Therapy, 10(1): 1–22.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B127" content-type="article"><label>127</label><element-citation publication-type="journal"><p>Caruso S, O’Brien DR, Cleary SP, et al., 2021, Genetics of Hepatocellular Carcinoma: Approaches to Explore Molecular Diversity. Hepatology, 73: 14–26.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B128" content-type="article"><label>128</label><element-citation publication-type="journal"><p>Jiang J, Pieterman CD, Ertaylan G, et al., 2019, The Application of Omics-Based Human Liver Platforms for Investigating the Mechanism of Drug-Induced Hepatotoxicity In Vitro. Applied Toxicology, 93: 3067–3098.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B129" content-type="article"><label>129</label><element-citation publication-type="journal"><p>Odagiri N, Matsubara T, Sato-Matsubara M, et al., 2021, Anti-Fibrotic Treatments for Chronic Liver Diseases: The Present and the Future. Cancer &amp; Hepatology, 27(3): 413.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B130" content-type="article"><label>130</label><element-citation publication-type="journal"><p>Ruman U, Fakurazi S, Masarudin MJ, et al., 2020, Nanocarrier-Based Therapeutics and Theranostics Drug Delivery Systems for Next Generation of Liver Cancer Nanodrug Modalities. International Journal of Nanomedicine, 1437–1456.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B131" content-type="article"><label>131</label><element-citation publication-type="journal"><p>Menyailo ME, Tretyakova MS, Denisov EV, 2020, Heterogeneity of Circulating Tumor Cells in Breast Cancer: Identifying Metastatic Seeds. International Journal of Molecular Sciences, 21(5): 1696.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B132" content-type="article"><label>132</label><element-citation publication-type="journal"><p>Tilsed C, 2021, How Does Chemotherapy Cure? Exploring and Exploiting the Immune System to Transform the Tumor Microenvironment and Improve Chemotherapy Efficacy, thesis, University of Western Australia.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B133" content-type="article"><label>133</label><element-citation publication-type="journal"><p>Lone SN, Nisar S, Masoodi T, et al., 2022, Liquid Biopsy: A Step Closer to Transform Diagnosis, Prognosis, and Future of Cancer Treatments. Molecular Cancer, 21(1): 79.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B134" content-type="article"><label>134</label><element-citation publication-type="journal"><p>Habli Z, AlChamaa W, Saab R, et al., 2020, Circulating Tumor Cell Detection Technologies and Clinical Utility: Challenges and Opportunities. Cancers, 12(7): 1930.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B135" content-type="article"><label>135</label><element-citation publication-type="journal"><p>Stejskal P, Goodarzi H, Srovnal J, et al., 2023, Circulating Tumor Nucleic Acids: Biology, Release Mechanisms, and Clinical Relevance. Molecular Cancer, 22(1): 15.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B136" content-type="article"><label>136</label><element-citation publication-type="journal"><p>Ribeiro IP, de Melo JB, Carreira IM, 2019, Head and Neck Cancer: Searching for Genomic and Epigenetic Biomarkers in Body Fluids–the State of Art. Molecular Cancer, 12(1): 33.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B137" content-type="article"><label>137</label><element-citation publication-type="journal"><p>Chen WH, Luo GF, Zhang XZ, 2019, Recent Advances in Subcellular Targeted Cancer Therapy Based on Functional Materials. Advanced Materials, 31(3): 1802725.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B138" content-type="article"><label>138</label><element-citation publication-type="journal"><p>Castro-Giner F, Aceto N, 2020, Tracking Cancer Progression: From Circulating Tumor Cells to Metastasis. Genomic Medicine, 12(1): 31.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B139" content-type="article"><label>139</label><element-citation publication-type="journal"><p>Compton C, Compton C, 2020, Cancer Initiation, Promotion, and Progression and the Acquisition of Key Behavioral Traits. Cancer: The Enemy from Within, Springer, Amsterdam, 25–48.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B140" content-type="article"><label>140</label><element-citation publication-type="journal"><p>Lin D, Shen L, Luo M, et al., 2021, Circulating Tumor Cells: Biology and Clinical Significance. Therapy, 6(1): 404.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B141" content-type="article"><label>141</label><element-citation publication-type="journal"><p>Słomka A, Wang B, Mocan T, et al., 2022, Extracellular Vesicles and Circulating Tumor Cells–Complementary Liquid Biopsies or Standalone Concepts? Therapy, 12(13): 5836.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B142" content-type="article"><label>142</label><element-citation publication-type="journal"><p>Sayed ZS, Khattap MG, Madkour MA, et al., 2024, Circulating Tumor Cells Clusters and Their Role in Breast Cancer Metastasis: A Review of Literature. Diagnostic Oncology, 15(1): 94.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B143" content-type="article"><label>143</label><element-citation publication-type="journal"><p>Chen F, Zhong Z, Tan H-Y, et al., 2020, The Significance of Circulating Tumor Cells in Patients with Hepatocellular Carcinoma: Real-Time Monitoring and Moving Targets for Cancer Therapy. Cancers, 12(7): 1734.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B144" content-type="article"><label>144</label><element-citation publication-type="journal"><p>Zhou J, Zhang Z, Zhou H, et al., 2020, Preoperative Circulating Tumor Cells to Predict Microvascular Invasion and Dynamical Detection Indicate the Prognosis of Hepatocellular Carcinoma. BioCell, 20: 1–10.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B145" content-type="article"><label>145</label><element-citation publication-type="journal"><p>Zubair M, Riaz M, Kiani MN, et al., 2024, Application of Nanotechnology for Targeted Drug Delivery and Nontoxicity. International Journal of Green Pharmacy and Nanomedicine, 2(2): 57–67.</p><pub-id pub-id-type="doi"/></element-citation></ref></ref-list></back></article>
