Role of Molecular and Genetic Profiling in Developing Targeted Therapies for Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers worldwide, with a pressing need for more effective therapeutic strategies. Molecular and genetic profiling have emerged as critical tools in understanding the complex heterogeneity of HCC. These approaches enable the identification of key genetic mutations, signaling pathways, and molecular subtypes, laying the foundation for the development of targeted therapies. Advances in next-generation sequencing (NGS) and high-throughput omics technologies have revealed actionable genetic alterations and epigenetic changes, such as those affecting TP53, CTNNB1, and the Wnt/\(\beta\)-catenin pathway, which have been instrumental in guiding personalized treatments. Furthermore, profiling techniques have identified biomarkers for patient stratification and predictors of therapeutic response, thereby improving clinical outcomes. Despite these advances, challenges remain in integrating molecular data into clinical practice, including tumor heterogeneity, resistance mechanisms, and the lack of reliable biomarkers. Recent innovations in computational biology and artificial intelligence (AI) are addressing these barriers, enhancing the accuracy of predictive models for drug response. Combining molecular profiling with immunotherapy has also shown promise, particularly with checkpoint inhibitors targeting PD-1/PD-L1 and CTLA-4. This paper explores the current state and future directions of molecular and genetic profiling in HCC, focusing on its role in developing targeted therapies. Key discussions include the identification of actionable genetic mutations, the application of multi-omics approaches, and the integration of precision medicine with immunotherapy. These advancements highlight the transformative potential of molecular profiling in achieving personalized treatment for HCC, ultimately improving survival rates and quality of life for patients.