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Volume 595 Issue 7869, 29 July 2021

Two strikes

Hepatocellular carcinoma (HCC) is one of the most common forms of liver cancer — and is also aggressive and very hard to treat. Patients who have advanced HCC are currently given a targeted therapy such as lenvatinib, a multi-kinase inhibitor. But lenvatinib has so far had only limited clinical success. In this week’s issue, René Bernards and his colleagues present the results of a CRISPR–Cas9 genetic screen that reveal a potential role for epidermal growth factor receptor (EGFR) in limiting the effectiveness of lenvatinib. Working first with animal models and then with 12 patients who had advanced HCC, the researchers found that administering gefitinib, which inhibits EGFR signalling, alongside lenvatinib generates a positive increase in response to the drug (illustrated on the cover by the idea that only those tumour cells that receive two drugs — symbolized by the arrows — are killed). The team suggests this could represent a promising strategy for treating HCC.

Cover image: Shuyang Zhou/Hangzhou Apex Digital Technology

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