Liver cancer ranks as one of the most common cancers in the world. A closer inspection on this type of cancer in South Korea reveals a significant overrepresentation of the disease. It is estimated that, on average, 16,000 people develop it every year and it contributes to 28.4 deaths per 100,000.
For how widespread liver cancer is, treating it is complicated. The drug known as Sorafenib is the only approved drug
|Professor Kwang-Hyun Cho
for the treatment of hepatocellular carcinoma (HCC), the most common type of primary liver cancer. However, it is reported that it only works on around 20% of medicated subjects, and a portion of these patients are acquiring resistance to it. Previously, researchers were unable to increase the efficacy of Sorafenib due to the lack of understanding regarding its action and resistance mechanisms.
However, Professor Kwang-Hyun Cho of the Department of Bio and Brain Engineering has changed that. Previously known for co-publishing the Encyclopedia of Systems Biology, Professor Cho conducted research alongside Professor Jung-Hwan Yoon from Seoul National University to further understand how Sorafenib operates at the cellular level.
Utilizing a systems approach, the research team analyzed the changes to messenger RNA (mRNA) in HCC cell lines due to the presence of Sorafenib and employed network analysis to examine the action and resistance mechanisms of the drug This use of systems biology analysis, which involves the modeling of complex biological systems through computations and mathematics backed by biological experiments, led the team to discover that the presence of the enzyme protein disulfide isomerase (PDI) affected the resistance mechanism of Sorafenib.
The analysis showed that blocking PDI leads to a significant increase in the efficacy of Sorafenib. Through both in vitro experimentation and in vivo trials on mice, the team discovered that the orally ingestible PDI inhibitor propynoic acid carbamoyl methyl amide (PACMA) 31 had synergic effects with Sorafenib. PACMA 31 allowed Sorafenib to have a greater effect on patients that showed resistance.
This research has not only helped establish a more effective method for the treatment of liver cancer; as Professor Cho asserted, it is also “a representative case of overcoming this limitation of traditional life science research by using a systems biology approach, combining IT and life science.”