Primary liver cancer is the second leading cause of cancerrelated death worldwide and therefore a major public health challenge. Primary liver cancer comprises hepatocellular.Carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and other rare tumors, notably fibrolamellar carcinoma and hepatoblastoma. The molecular and clinical features of HCC versus iCCA are distinct, but these conditions have overlapping risk factors and pathways of oncogenesis.Pathway targeting in HCC has thus far mostly been limited to inhibiting angiogenesis. While several lines of investigation target epidermal growth factor receptor and vascular endothelial growth factor receptor (EGFR and VEGFR, respectively), these are at best still quite exploratory.
The Raf/MEK/ERK pathway has also been implicated in HCC tumorigenesis. Raf (receptor activation factor) kinase regulates the mitogen-activated protein (MAP) kinase signaling pathway, a key to cellular functions such as growth, transformation, and apoptosis. MEK1 overexpression in HCC cell lines has been shown to enhance tumor growth and survival by preventing apoptosis.This suggests a potential therapeutic role for Raf kinase and MEK inhibitors.

References

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