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.
肝脏是人体主要的代谢器官，负责营养物质和药物的代谢。晚期肝病会导致肝脏代谢功能受损。由于肝脏无法产生有效的药物代谢产物和/或无法正常灭活药物，导致药物毒性较高，患者依从性随之降低，因此这些疾病通常难以通过药物治疗。肝细胞癌（HCC）是一种在纤维化/肝硬化肝脏上发展的疾病，大多在晚期才被诊断出来。目前治疗晚期HCC的方案包括免疫疗法或酪氨酸激酶抑制剂（TKIs）的联合应用，但仅能提供约2年的生存获益。此外，免疫疗法仅对27%的HCC患者有效，而接受TKIs治疗的患者在6个月内必然会产生耐药性。在此背景下，基因疗法作为一种替代方法，可能为HCC患者带来显著益处。尽管针对HCC或其他肝脏疾病的基因疗法尚未获得美国食品药品监督管理局（FDA）的批准，但该领域近年来已取得重大进展。在这篇综述文章中，我们重点介绍了最新文献，展示了基因疗法在管理HCC患者、延长生存获益以及提高生活质量方面的潜力。
Gene Therapy Strategies for Hepatocellular Carcinoma (HCC): Current Landscape and Future Directions
肿瘤(癌症)患者之家