Fig. 6: NF1 alterations is common in cancers.
From: Genome-scale CRISPR-Cas9 knockout screening in hepatocellular carcinoma with lenvatinib resistance
A NF1 alterations in cancers. NF1 somatic mutation frequency showed in cBioPortal cancer datasets was 6.1%. B NF1 altered in multiple cancers. The NF1 altered in 5.42% of 392 HCC cases. C NF1 altered patients had poorer outcomes compared to unaltered patients. D A schematic depicting the suggested mechanism. Lenvatinib exerts its anticancer effect by inhibiting PI3K/AKT and MEK/ERK signaling pathways through target receptor tyrosine kinase. NF1 loss can active Akt and ERK phosphorylation, and DUSP9 loss can active ERK phosphorylation, further induces FOXO3 phosphorylation, leading to degradation of FOXO3, finally resulting in the progression of HCC. Trametinib, a small-molecule protein kinase inhibitors target MEK, can still inhibit the progression of HCC even NF1 loss by inhibited Akt and ERK phosphorylation.
