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Fonseca et al. Hepatoma Res 2023;9:27 Hepatoma Research
DOI: 10.20517/2394-5079.2023.63

Editorial Open Access

Current landscape and future directions for systemic

treatments of hepatocellular carcinoma

1
Leonardo G. Fonseca , Flair J. Carrilho 2
1
Clinical Oncology, Instituto do Cancer do Estado de São Paulo, Hospital das Clínicas, University of São Paulo School of Medicine,
São Paulo 05403-000, Brazil.
2
Division of Clinical Gastroenterology and Hepatology, Hospital das Clínicas, Department of Gastroenterology, University of São
Paulo School of Medicine, São Paulo 05403-000, Brazil.
Correspondence to: Dr. Leonardo G. Fonseca, Department of Clinical Oncology, Instituto do Cancer do Estado de Sao Paulo,
University of São Paulo School of Medicine, Av Dr Arnaldo 251, Sao Paulo, ZIP 05403-000, Brazil. E-mail: l.fonseca@fm.usp.br
How to cite this article: Fonseca LG, Carrilho FJ. Current landscape and future directions for systemic treatments of
hepatocellular carcinoma. Hepatoma Res 2023;9:27. https://dx.doi.org/10.20517/2394-5079.2023.63

Received: 5 Jun 2023 Accepted: 20 Jun 2023 Published: 21 Jun 2023
Academic Editor: Giuliano Ramadori Copy Editor: Yanbing Bai Production Editor: Yanbing Bai

Systemic treatment is the optimal approach for patients with advanced or intermediate-stage hepatocellular
carcinoma (HCC) with contraindications or refractoriness to locoregional treatments[1]. The aim of systemic
treatment is to prolong survival and delay clinical deterioration. Until 2008, no systemic therapy provided
meaningful clinical benefit. In the past, studies that evaluated the role of conventional chemotherapy,
mainly doxorubicin or combinations of platinum agents, resulted in significant toxicities, without a clear
demonstration of efficacy[2].

In the early 2000s, there were advances in the knowledge of the molecular mechanisms that drive
hepatocarcinogenesis, such as the hyperactivation of intracellular signaling pathways of protein kinases and

angiogenesis[3]. This knowledge has boosted the development of molecular target drugs that inhibit

receptors and mediators of these signaling pathways, which have been translated into clinical studies that
included patients with advanced HCC.
Sorafenib, a multikinase inhibitor, was the first systemic agent to demonstrate a survival benefit in patients
with unresectable HCC based on two placebo-controlled trials[4,5]. It is important to highlight that this drug
increased survival without causing a significant reduction in tumor burden. The radiological response rate,
© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0
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