1Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université de Paris Cité, Team «Functional Genomics of Solid Tumors», 75006 Paris, France.
2Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, 75006 Paris, France.
3Internal Medicine and Hepatology Unit, Department of Experimental and Clinical Medicine, University of Firenze, 50134 Firenze, Italy.
4Hôpital Européen Georges Pompidou, APHP, 75015 Paris, France.
5Liver Unit, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, 93000 Bobigny, France.
6Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris Nord, 93000 Bobigny, France.
Hepatocellular carcinoma (HCC) accounts for 90% of primary hepatic malignancies and is one of the major causes of cancer-related death. Over the last 15 years, the molecular landscape of HCC has been deciphered, with the identification of the main driver genes of liver carcinogenesis that belong to six major biological pathways, such as telomere maintenance, Wnt/b-catenin, P53/cell cycle regulation, oxidative stress, epigenetic modifiers, AKT/mTOR and MAP kinase. The combination of genetic and transcriptomic data composed various HCC subclasses strongly related to risk factors, pathological features and prognosis. However, translation into clinical practice is not achieved, mainly because the most frequently mutated genes are undruggable. Moreover, the results derived from the analysis of a single tissue sample may not adequately catch the intra- and intertumor heterogeneity. The analysis of circulating tumor DNA (ctDNA) is broadly developed in other types of cancer for early diagnosis, prognosis and monitoring under systemic treatment in order to identify primary and secondary mechanisms of resistance. The aim of this review is to describe recent data about the HCC molecular landscape and to discuss how ctDNA could be used in the future for HCC detection and management.