Abstract

Abstract Hepatocellular carcinoma (HCC) is a highly heterogeneous cancer, both at the molecular and histological level. High-throughput sequencing and gene expression profiling have identified distinct transcriptomic subclasses and recurrently altered cancer driver genes. Several HCC subtypes characterized by histological features have also been identified. HCC phenotype appears to be closely related to particular gene mutation and driven by various oncogenic pathway alterations. Identification of the origin of HCC development and their trajectory of progression is important to understand tumor evolution and to identify the mechanisms of tumor response or resistance to therapies. We will review the early and late molecular alterations driving HCC occurrence and progression of tumors in the context of patient lifespan and exposure to environmental factors. Several questions remain to be answered, in particular on the identification of the cells at the origin of the malignant transformation into HCC and the mechanism of escape to the immunological monitoring. Citation Format: Jessica Zucman-Rossi. Molecular drivers in hepatocellular carcinoma: The story of what we know and what are we missing [abstract]. In: Proceedings of the AACR Special Conference: Advances in the Pathogenesis and Molecular Therapies of Liver Cancer; 2022 May 5-8; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(17_Suppl):Abstract nr IA01.

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