Year: 2024
Type: article
Abstract: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with an estimated 750,000 deaths in 2022. Recent emergence of molecular targeted agents and immune checkpoint inhibitors and their combination therapies have been transforming HCC care, but their prognostic impact in advanced-stage disease remains unsatisfactory. In addition, their application to early-stage disease is still an unmet need. Omics profiling studies have elucidated recurrent and heterogeneously present molecular aberrations involved in pro-cancer tumor (immune) microenvironment that may guide therapeutic strategies. Recurrent aberrations such somatic mutations in TERT promoter and TP53 have been regarded undruggable, but recent studies have suggested that these may serve as new classes of therapeutic targets. HCC markers such as alpha-fetoprotein, glypican-3, and epithelial cell adhesion molecule have also been explored as therapeutic targets. These molecular features may be utilized as biomarkers to guide the application of new approaches as companion biomarkers to maximize therapeutic benefits in patients who are likely to benefit from the therapies, while minimizing unnecessary harm in patients who will not respond. The explosive number of new agents in the pipelines have posed challenges in their clinical testing. Novel clinical trial designs guided by predictive biomarkers have been proposed to enable their efficient and cost-effective evaluation. These new developments collectively facilitate clinical translation of personalized molecular-targeted therapies in HCC and substantially improve prognosis of HCC patients.
Source: Journal of Liver Cancer
Institution: The University of Texas Southwestern Medical Center
Language: English
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
Awards: G152670155, G1908746083, A Novel Risk Stratification and Early Detection Strategy to Reduce Liver Cancer Mortality, G3796334057, Recruitment of Rising Stars, G5217097218, G5702072450, G660960757, G789344179, G9000235369, G9000274696, G9000317306, G9000339245, G9000343836, UT Southwestern NORC, UT Southwestern Medical Center Simmons Comprehensive Cancer Center
OpenAlex ID: W4405124907