Abstract
Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality globally, presenting significant challenges in treatment due to tumor heterogeneity, drug resistance, and limitations of conventional preclinical models. Human-induced pluripotent stem cells (hiPSCs) offer a transformative platform for addressing these issues. Derived from adult somatic cells, hiPSCs possess pluripotency and self-renewal capabilities, enabling the generation of patient-specific and genetically engineered liver models, including two-dimensional hepatocyte-like cells and more physiologically relevant three-dimensional liver organoids. These hiPSC-derived models are revolutionizing drug development by facilitating high-throughput drug screening, improving the prediction of drug-induced liver injury (DILI), enabling personalized medicine approaches, and elucidating complex disease mechanisms. Despite challenges such as cost, cell maturation state, and scalability, ongoing advancements in culture techniques, microfluidics, and integration with artificial intelligence promise to further enhance the utility of hiPSC technology, holding immense potential for accelerating the discovery of novel therapies and improving patient outcomes in liver cancer.