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Review
. 2007 Dec 28;13(48):6470-7.
doi: 10.3748/wjg.v13.i48.6470.

AKT and ERK1/2 signaling in intrahepatic cholangiocarcinoma

K J Schmitz  1 , H Lang, J Wohlschlaeger, G C Sotiropoulos, H Reis, K W Schmid, H A Baba
Affiliations
Review

AKT and ERK1/2 signaling in intrahepatic cholangiocarcinoma

K J Schmitz et al. World J Gastroenterol. .

Abstract

Intrahepatic cholangiocarcinomas (ICC) are neoplasms that originate from cholangiocytes and can occur at any level of the biliary tree. Surgical resection is the current therapy of choice for this highly aggressive cancer. However, the 5-year survival still is poor, with high recurrence rates. Due to the intrahepatic growth a significant proportion of patients present with advanced disease and are not candidates for curative surgery or transplantation. The existing palliative options are of limited benefit and there is a great necessity for novel therapeutic options. In this article we review the role of the phosphoinositide 3-kinase(PI3K)/AKT and extracellular regulated kinase (ERK) signaling pathways in ICC and present new data on the prognostic value of these protein kinases. Finally, we discuss future upcoming therapeutic options based on targeting these signaling pathways.

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Figures

Figure 1
Figure 1
Overview of the AKT and ERK signaling pathway.
Figure 2
Figure 2
Light micrograph displaying strong phospho-ERK1/2 (A) and strong phospho-AKT (B) expression as analyzed by immunohistochemistry in intrahepatic cholangiocarcinoma (x 400).
Figure 3
Figure 3
Kaplan-Meier survival plot for disease specific overall survival in the complete series of 62 intrahepatic cholangiocarcinoma in relation to pERK immunostaining intensity. Log-rank test: P = 0.242.
Figure 4
Figure 4
Kaplan-Meier survival plot for disease specific overall survival in the complete series of 59 intrahepatic cholangiocarcinoma in relation to pAKT immunostaining intensity. Log-rank test: P = 0.618.
Figure 5
Figure 5
Intrahepatic cholangiocarcinoma with positive EGFR expression exhibit significantly more frequent AKT activation (χ2 analysis: P = 0.028).
See this image and copyright information in PMC

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