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| Synergistic effects of anti-angiogenesis and immune checkpoint blockade - a new era of systemic chemotherapy for hepatocellular carcinoma |
| Yuji Eso ∗, Hiroshi Seno |
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
∗ Corresponding author.
E-mail address: yujieso@kuhp.kyoto-u.ac.jp (Y. Eso). |
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Abstract Tumor growth requires oxygen and nutrient supplementation through angiogenesis from preexisting vascular beds. Hepatocellular carcinoma (HCC) is a hyper-vascularized tumor with a predominant arterial blood flow. Therefore, targeting angiogenesis is essential for treating HCC. Currently approved molecular-targeted agents (MTAs) for HCC affect angiogenic pathways. Sorafenib, which was approved as the first MTA in 2008, targets vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), c-Kit, and Raf kinases [1]. Sorafenib has a high incidence of adverse events (AEs) that impair quality of life, such as hand-foot skin reaction and diarrhea. Therefore, novel tolerable and effective first-line MTAs and second-line MTAs after sorafenib failure were desired. Lenvatinib was approved as a novel first-line treatment in 2018 [2], and regorafenib and ramucirumab were approved as second-line treatments in 2017 and 2019, respectively [3,4].
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2021, Vol. 20 
