Abstract
THERAPIES TARGETING NOTCH SIGNALING PATHWAY IN HEPATOCELLULAR CARCINOMA

Nirmala Subramaniam, Pugazhendhi K., Ashok Kumar K., Devaki Thiruvengadam*

ABSTRACT

Hepatocarcinoma ranks third among much prevailing cancer globally expressing high mortality rates. Intake of alcoholic beverages and chemical agent aflatoxin, hepatitis B, C viruses and inborn error are some of the prominent risk factors for Hepatocellular carcinoma (HCC). A majority of 80% of HCC patients is seen with liver cirrhosis and fibrosis. Treatment of HCC includes surgical resection, liver transplantation, chemoembolization, percutaneous ablation, radiofrequency ablation and sorafenib is one of the novel chemotherapy. These therapies effectively prolong the survival rate in advanced stage. Even though, many therapies can treat HCC, the introduction of alternative chemotherapeutic drugs which especially targets the tumor must be developed and alteration in cellular signaling pathway causes hepatocarcinogenesis. Interesting, by focusing these pathways the tumorigenesis can be prevented. Notch system is one of the cell signaling pathways. Notch cellular signal is extremely conserved and it occupies a vital part in determining the cell destiny, rapid multiplication of cells, specialization and programmed cell death in tissues. Dysregulation of Notch leads to abnormal expression of Notch gene. In cancerous cells, Notch is overexpressed leading to increase in the proliferation and decrease in apoptosis. Gamma secretase inhibitor (GSIs) inhibits Notch signaling. Also, several decoys, monoclonal antibodies can block notch activating signal. In HCC, GSIs successfully inhibits tumor growth. Notch targets in HCC have become a challenging therapeutic tool. In this follow-up, Notch signal system in HCC is explored along with its emerging tool targeting gamma-secretase complex.

Keywords: Hepatocellular carcinoma, Notch signaling, Gamma-secretase inhibitor, Chemotherapeutic drugs.


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