The number of liver cancer has more than tripled in the past 20 years in the United States. Texas has the highest death rate from HCC in the nation. Patients' survival rate is very low due to very limited treatment methods. At the same time, the rate of obesity, and its related metabolic disease, such as fatty liver, is also increasing. These are major modifiable risk factors for HCC development. In Texas, the obesity rate is currently 33%, with 30% of the population having fatty liver disease. Thus, discovering novel HCC drug treatments for obesity/fatty liver related condition is of high priority in Texas. Nuclear receptor CAR has been found to promote liver cancer development in mice. Th...

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The number of liver cancer has more than tripled in the past 20 years in the United States. Texas has the highest death rate from HCC in the nation. Patients' survival rate is very low due to very limited treatment methods. At the same time, the rate of obesity, and its related metabolic disease, such as fatty liver, is also increasing. These are major modifiable risk factors for HCC development. In Texas, the obesity rate is currently 33%, with 30% of the population having fatty liver disease. Thus, discovering novel HCC drug treatments for obesity/fatty liver related condition is of high priority in Texas. Nuclear receptor CAR has been found to promote liver cancer development in mice. There are 18% of human HCC patients have high CAR expression in the tumor. We found that CAR inhibitor reduces HCC in mice, mainly because of suppressing the cancer cell lipid-making machinery. In the meanwhile, we found CAR regulates the expression of many lipid-making genes. Lipids are an important energy source and building blocks of cancer cells. Fatty liver related HCC, which is very common in TX, usually has a high background of lipid synthesis. Thus, in this proposal, our goals are to test if CAR is important in this type of fatty liver related HCC, and if CAR inhibitor are effective in treating this "fatty" HCC. Our research will open a new window for the treatment of fatty liver related HCC. Inhibiting the gene CAR by its inhibitor in "fatty" HCC is similar to hormonal therapy in breast cancer and prostate cancer. Our study will further uncover the fatty" HCC as a specific subtype that is highly responsive to CAR inhibitor treatment. The success of our research would contribute major insights into the discovery of novel treatments of the fatty liver associated HCC, which is prevalent in Texas."

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