Date of Award

2016

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Molecular and Cellular Biochemistry Program

Abstract

Hepatocellular Carcinoma is the second most lethal cancer after pancreatic cancer. Unresectable HCC tumors carry a poor prognosis and few treatment options are available. The dismal prognosis is mainly due to limited therapy options and molecularly targeted therapy is deemed as solution. Here, we report a novel role of c-Abl in HCC development. We provide evidence of c-Abl activation in human HCC samples compared to normal liver. Using genetic and pharmacological tools, we show that c-Abl plays a vital role in HCC progression in vitro and in vivo. We have identified Axl as an effector in processes mediated by c-Abl. Our findings also show that c-Abl inhibition has synergistic effects with Sorafenib treatment and that this synergism occurs because Sorafenib induces activation of both c-Abl and Axl. Taken together, these data we have thus far provide evidence for c-Abl as a critical HCC oncogenic driver which can be targeted pharmacologically.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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