{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T19:46:32Z","timestamp":1791747992759,"version":"4.3.4"},"reference-count":205,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T00:00:00Z","timestamp":1728432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Liver cancer represents a substantial global health challenge, contributing significantly to worldwide morbidity and mortality. It has long been understood that tumors are not composed solely of cancerous cells, but also include a variety of normal cells within their structure. These tumor-associated normal cells encompass vascular endothelial cells, fibroblasts, and various inflammatory cells, including neutrophils, monocytes, macrophages, mast cells, eosinophils, and lymphocytes. Additionally, tumor cells engage in complex interactions with stromal cells and elements of the extracellular matrix (ECM). Initially, the components of what is now known as the tumor microenvironment (TME) were thought to be passive bystanders in the processes of tumor proliferation and local invasion. However, recent research has significantly advanced our understanding of the TME\u2019s active role in tumor growth and metastasis. Tumor progression is now known to be driven by an intricate imbalance of positive and negative regulatory signals, primarily influenced by specific growth factors produced by both inflammatory and neoplastic cells. This review article explores the latest developments and future directions in understanding how the TME modulates liver cancer, with the aim of informing the design of novel therapies that target critical components of the TME.<\/jats:p>","DOI":"10.3390\/cells13191666","type":"journal-article","created":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T06:30:03Z","timestamp":1728455403000},"page":"1666","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Beyond Cancer Cells: How the Tumor Microenvironment Drives Cancer Progression"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9021-8334","authenticated-orcid":false,"given":"Hussein","family":"Sabit","sequence":"first","affiliation":[{"name":"Department of Medical Biotechnology, College of Biotechnology, Misr University for Science and Technology, Giza P.O. Box 77, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9793-0970","authenticated-orcid":false,"given":"Borros","family":"Arneth","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Hospital of the Universities of Giessen and Marburg (UKGM), Philipps University Marburg, Baldinger Str., 35043 Marburg, Germany"},{"name":"Institute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Hospital of the Universities of Giessen and Marburg (UKGM), Justus Liebig University Giessen, Feulgenstr. 12, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3883-2000","authenticated-orcid":false,"given":"Shaimaa","family":"Abdel-Ghany","sequence":"additional","affiliation":[{"name":"Department of Environmental Biotechnology, College of Biotechnology, Misr University for Science and Technology, Giza P.O. Box 77, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Engy F.","family":"Madyan","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology, College of Biotechnology, Misr University for Science and Technology, Giza P.O. Box 77, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashraf H.","family":"Ghaleb","sequence":"additional","affiliation":[{"name":"Department of Surgery, College of Medicine, Misr University for Science and Technology, Giza P.O. Box 77, Egypt"},{"name":"Department of Surgery, College of Medicine, Cairo University, Giza 12613, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3130-0551","authenticated-orcid":false,"given":"Periasamy","family":"Selvaraj","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong M.","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramireddy","family":"Bommireddy","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Elhashash","sequence":"additional","affiliation":[{"name":"Department of Biology, Texas A&M University, 3258 TAMU I, College Station, TX 77843-3258, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e002467","DOI":"10.1136\/jitc-2021-002467","article-title":"Tumor microenvironment evaluation promotes precise checkpoint immunotherapy of advanced gastric cancer","volume":"9","author":"Zeng","year":"2021","journal-title":"J. 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