Fig. 8: Schematic illustration of the mechanisms here elucidated as responsible for the loss of lenvatinib efficacy in human HCC. | Acta Pharmacologica Sinica

Fig. 8: Schematic illustration of the mechanisms here elucidated as responsible for the loss of lenvatinib efficacy in human HCC.

From: Hepatocellular carcinoma cells loss lenvatinib efficacy in vitro through autophagy and hypoxia response-derived neuropilin-1 degradation

Fig. 8

Through autophagy, (1) lenvatinib promotes NRP1 degradation and strongly decreases cell proliferation and migration. (2) Hypoxic conditions act by inducing autophagy and, therefore, NRP1 degradation, but also the higher expression of HIF-1α raised NRP1 protein levels. (3) When autophagy is inhibited by bafilomycin A1, NRP1 levels increase and the antitumor actions of lenvatinib experience a reduction, increasing proliferation and migration abilities of HCC cells. Targeting not only (4) NRP1, but also (5) HIF-1α, enhances antitumor effects of lenvatinib and could prevent therapeutic failure derived from autophagy inhibition by HCC cells. This figure was created with BioRender.com.

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