Date of Award
Master of Science (MS)
Molecular and Cellular Biochemistry Program
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.
Chitsike, Lennox, "The Role of c-Abl Kinase in HCC Development" (2016). Master's Theses. 3259.
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.
Copyright © 2016 Lennox Chitsike
Available for download on Thursday, December 06, 2018