Hepatocellular carcinoma: Causes, putative biomarkers, and current therapies

Recent advances in molecular diagnostic technologies continue to facilitate the discovery of diverse cellular signaling pathways that are involved in the development and progression of hepatocellular carcinoma (HCC). HCC accounted for 30,000 cancer-related deaths in the United States (U.S.) in 2020. In the era of personalized medicine that has led to improved therapies for many cancers, the efficacy of current anti-HCC therapies remains modest at best. Although significant advances in basic science research have identified alterations of cellular, genetic, and epigenetic signals that influence HCC development, and some of these have led to the development of anti-HCC therapies, overall, HCC cures continue to be elusive. Moreover, tumor-related changes in the microbiome and the tumor microenvironment have been identified and have revealed multiple potential pathways that can either aid in diagnosing HCC or serve as new therapeutic targets. However, even here, there is a need to translate these observations into a clinical outcome, and HCC typically has a poor prognosis. In any clinical scenario, the clinical oncologist starts by identifying risk factors, followed by using diagnostic tools, including testing for specific biomarkers, to help diagnose the stage of the disease, which aids in selecting the best treatment options to improve the patient’s prognosis. In this review, we will follow a similar pathway by first providing a description of HCC risk factors, biomarkers, and diagnostic tools and then discussing treatment options. Rather than provide a historical review, we will focus on the most current HCC biomarkers and treatments that have been published and will integrate the results of recent basic science research on cellular signals that are altered in HCC, especially where these have contributed to novel HCC therapies.