Gene Therapy for Hepatocellular Carcinoma: Highlighting the Journey from Theory to Clinical Applications

Treatment for hepatocellular carcinoma (HCC) is currently limited to early stages where surgical intervention is applicable. Meanwhile, the response for most chemotherapies is still low, leaving patients in advanced stages without an effective therapeutic approach. Other therapeutic strategies based on immunotherapies or radiotherapy have a narrow spectrum with multiple limitations. These collective drawbacks necessitate the development of alternative strategies. Gene therapy has achieved a breakthrough in the treatment of several diseases, especially tumors. In the current review, a discussion is provided on the various strategies that have been developed for HCC gene therapy, the functional and genetic materials used, and their diverse delivery systems, with a special focus on novel targeting strategies based on biomaterials, peptide libraries, and aptamers. In addition, animal models that have been used in preclinical evaluation of HCC gene therapies are highlighted and compared. Lastly, ongoing clinical trials and future perspectives for these strategies are discussed. Hepatocellular carcinoma (HCC) is a global leading cause of death with limited therapeutic options. Gene therapy holds a promise for the treatment of HCC. In the current review, treatment modalities, gene targets, targeting methods, delivery vectors, combinations, and the animal models used for their evaluation are discussed. The ongoing clinical trials of these therapies are highlighted.