AsianScientist (Sep. 12, 2017) – Using a systems biology approach, researchers have improved on an existing liver cancer treatment. Their findings have been published in Hepatology.
Liver cancer is the fifth and seventh most common cancer found in men and women throughout the world, which makes it the second most common cause of cancer deaths. Liver cancer is known to carry the highest social cost in comparison to other cancers and it causes the highest fatality in earlier age groups (40s-50s), making it necessary to develop new treatments that mitigate side effects yet elevate the survival rate.
Sorafenib is a targeted anticancer drug approved by the FDA to treat progressive liver cancer patients. However, it is effective only in about 20 percent of the treated patients and only extends the survival rate of terminal cancer patients by less than three months on average. Also, acquired resistance to Sorafenib is emerging. The mechanism of resistance in cancer cells to Sorafenib remains largely unknown.
In this study, Professor Cho Kwang-Hyun at the Korea Advanced Institute of Science and Technology collaborated with Professor Yoon Jung-Hwan at Seoul National University Hospital to analyze the expression changes of genes in cancer cell lines treated with Sorafenib.
The team used a systems biology approach, combining computer simulations and biological experiments to reveal that protein disulfide isomerase (PDI) plays a crucial role in the resistance mechanism of Sorafenib and that Sorafenib efficacy can be improved significantly by blocking PDI.
In mouse models, the research team demonstrated the synergic effect of PDI inhibition with Sorafenib on killing liver cancer cells. Also, PDIs were found to be more highly expressed in tissues from patients whose cancers are resistant to Sorafenib. The team further confirmed these findings from clinical data through a retrospective cohort study.
“Molecules that play an important role in cell lines are mostly under complex regulation. This makes it difficult to study their underlying functions using conventional molecular approaches,” Cho said. “By using a systems biology approach, based on network analysis of cancer cells response to targeted therapy, we have developed a new treatment that overcomes drug resistance.”
The article can be found at: Won et al. (2017) Protein Disulfide Isomerase Inhibition Synergistically Enhances the Efficacy of Sorafenib for Hepatocellular Carcinoma.
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Source: Korea Advanced Institute of Science and Technology; Photo: Shutterstock.
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