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Program Co-Leaders |
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Hepatobiliary malignancies are a major cause of death worldwide, representing the fifth leading cause of cancer-related mortality. In almost all cases, hepatobiliary malignancies arise from chronic underlying hepatobiliary disease, especially viral hepatitis. The mission of the Liver Cancer Program is to support and stimulate basic, clinical, and population science research in liver cancer and to facilitate translation of these findings to a better understanding of risk, prevention, and therapy of hepatocellular carcinoma (HCC). The program's multidisciplinary group of more than 20 investigators includes researchers in basic science, population science, and clinical sciences, representing the fields of surgery, gastroenterology, and medical oncology.
Specifically, the program's translational research objectives are to:
Understand the factors influencing risk for viral hepatitis infection
While ongoing UCSF research focuses on basic-science studies of hepatitis B and D and epidemiology and treatment of hepatitis C, over the last two years there has been an increasing emphasis on patient-oriented research in studies of hepatitis B and on risk and prevention of hepatitis C. In particular, large population-based research studies are examining the risk of sexual transmission of hepatitis C and racial differences in response to hepatitis C treatment. Other researchers are investigating replication of the hepatitis D virus and immune pathogenesis of liver disease from the hepatitis B virus.
Understand the factors related to progression of hepatitis in the development of hepatocellular cancer
Although it is well established that viral hepatitis and subsequent cirrhosis are risk factors for hepatocellular carcinoma, very little is understood about the relative contributions of these processes to the development of hepatocellular cancer. Liver Cancer Program members have focused on the cellular molecular mechanisms of fibrosis and cell matrix interactions and have recently expanded studies to include nonalcoholic steatohepatitis-related metabolic disturbances such as glucose homeostasis, hyperlipidemia, insulin resistance, and PPAR intracellular signaling.
Understand biologic events in early oncogenesis of hepatocellular cancer
Research in human disease must evolve with a better understanding of risk and progression before clinical studies focusing on early biologic events can be designed. Researchers often undertake studies of animal models to look at specific biologic mechanisms. Researchers in the Liver Cancer Program have developed a transgenic mouse with liver-specific expression of the tetracycline transactivator protein, in which a gene of interest can be introduced under close observation and regulation. This model, which involves the conditional over-expression of c-MET, the receptor for hepatocyte growth factor, exhibits liver tumors that mimic HCC and can lead to new insights on human cancer.
Develop new paradigms for targeted therapeutics in prevention and treatment based on a better understanding of the biologic basis of hepatocellular cancer
Longstanding UCSF research has focused on regional therapy for liver malignancies, including chemo-embolization and the regional use of viral therapies (both cytolytic virus and adenovirus selected as vectors for gene-based therapy). New studies will look at regulation of the adenovirus receptor for the use of therapeutic adenoviruses in HCC. In addition, technological developments in immunoliposomal therapy, first introduced by researchers in the Breast Oncology Program, are expected to be adopted for appropriate targets involving hepatocellular cancer.
