{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T22:57:17Z","timestamp":1785538637239,"version":"3.56.0"},"reference-count":187,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T00:00:00Z","timestamp":1762560000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Institute","award":["P01CA275740"],"award-info":[{"award-number":["P01CA275740"]}]},{"name":"National Cancer Institute","award":["R01CA230561"],"award-info":[{"award-number":["R01CA230561"]}]},{"name":"National Cancer Institute","award":["R01CA244993"],"award-info":[{"award-number":["R01CA244993"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The liver is the primary metabolic organ in the body, metabolizing nutrients and drugs. Advanced liver diseases result in compromised metabolic function of the liver. These diseases are often difficult to treat with drugs because of inability of the liver to generate effective drug metabolites and\/or to properly inactivate the drugs resulting in high drug-induced toxicity with subsequent reduced patient compliance. Hepatocellular carcinoma (HCC) is a disease that develops on a fibrotic\/cirrhotic liver and is mostly diagnosed at an advanced stage. Current protocol for treating advanced HCC includes a combination of immunotherapy or tyrosine kinase inhibitors (TKIs), which provides a survival benefit of only ~2 years. In addition, immunotherapy is effective in only 27% of HCC patients and patients treated with TKIs invariably develop drug resistance within 6 months. In this scenario gene therapy serves as an alternative approach that might bring significant benefits to HCC patients. Although gene therapy approaches for HCC or other liver diseases have yet to obtain approval from the Food and Drug Administration (FDA), a significant advancement has been made over the years in this field. In this review article, we highlight very recent literature showing the promise of gene therapy in managing HCC patients, extending survival benefits and providing improved quality of life.<\/jats:p>","DOI":"10.3390\/cancers17223608","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T11:47:27Z","timestamp":1762775247000},"page":"3608","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Gene Therapy Strategies for Hepatocellular Carcinoma (HCC): Current Landscape and Future Directions"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5973-8347","authenticated-orcid":false,"given":"Ali Gawi","family":"Ermi","sequence":"first","affiliation":[{"name":"Department of Cellular, Molecular and Genetic Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rabha M.","family":"Younis","sequence":"additional","affiliation":[{"name":"Department of Cellular, Molecular and Genetic Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayla","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0973-2323","authenticated-orcid":false,"given":"Devanand","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Department of Cellular, Molecular and Genetic Medicine, Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1056\/NEJMra1001683","article-title":"Hepatocellular carcinoma","volume":"365","year":"2011","journal-title":"N. 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