Emerging role of molecular diagnosis and personalized therapy for hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a prevalent malignancy worldwide, ranking as the sixth most common malignancy and the third leading cause of cancer-related mortality. Late diagnosis, limited management options, and its complex etiology contribute to the poor prognosis and high mortality rates. Recent advances in understanding the molecular mechanisms of HCC and innovations in high-throughput sequencing technologies have led to the development of molecular diagnostics and personalized therapies for this challenging malignancy. This review provides a comprehensive overview of research on the molecular diagnosis and individualized treatment for HCC. We highlight key advances and potential future directions and discuss the application of next-generation sequencing technologies to identify and characterize genetic and epigenetic alterations in HCC patients. These technologies may aid in the selection of targeted therapies, prediction of treatment response, and monitoring disease progression. Furthermore, we explore the role of liquid biopsy in HCC diagnosis, prognosis prediction, and treatment monitoring, focusing on circulating tumor cells, circulating tumor DNA, and extracellular vesicles. We also explore the evolving landscape of personalized therapy for HCC, including targeted therapies against key oncogenic signaling pathways, immune checkpoint inhibitors, tumor-agnostic therapies, and innovative cell-based therapies. We discuss the challenges and opportunities that lie ahead in the quest to improve HCC patient outcomes through the integration of molecular diagnostics and individualized precision therapies. We emphasize the need for multi-interdisciplinary collaboration, refinement of predictive and prognostic biomarkers, and the development of more effective combination strategies for HCC management in the new area of precision medicine.

Keywords: Diagnosis; Hepatocellular carcinoma; Immune checkpoint inhibitors; Liquid biopsy; Targeted therapy.

Fig. 1

Comprehensive overview of the current state of molecular diagnosis and individualized treatment regimens for HCC. HCC, hepatocellular carcinoma; ctDNA, circulating tumor DNA; ncRNA, non-coding RNA; miRNA, microRNA; lncRNA, long non-coding RNA; CTC, circulating tumor cell; NGS, next-generation sequencing.