DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

Posted October 17, 2017

Liver Cancer is a Deadly Disease in the United States and Abroad

According to the World Health Organization, liver cancer is the second most common cause of cancer-related death worldwide.1 In the United States, liver cancer is relatively rare, with only 1% of the population at risk of developing this type of cancer. However, the incidence of liver cancer and liver cancer-related death in the United States has been on an alarming, rise for decades2 making liver cancer a public health concern.

The liver is a critical organ used by the body to detoxify the blood, produce compounds to facilitate digestion, store nutrients for later use, and many other important functions. Liver cancer refers to cancer that has originated within this organ and should not to be confused with liver metastases, which are tumors found in the liver that originated elsewhere. For cancer originating from the liver, there are two major types: hepatocellular carcinoma (HCC), which arises from the liver cells themselves, and cholangiocarcinoma, which occurs within the tubes that carry bile to and from the liver. Chronic injury resulting in cirrhosis, or scarring of the liver, is the number one risk factor for developing liver cancer; the majority of liver cancer patients have some evidence of cirrhosis. Cirrhosis can stem from any liver injury, but is widely associated with viral hepatitis and heavy alcohol usage.3

There are many confounding factors that obstruct progress towards understanding and treating this lethal disease. One major hurdle is that the majority of patients diagnosed with liver cancer are identified after their cancer has progressed beyond a point where tumor resection is advised.4 These patients are left with few treatment options, and their prognosis tends to be poor. Novel therapeutic regimes to combat liver cancer in its intermediate and advanced stages are of critical need for this community. Alternatively, identifying those individuals at risk of developing liver cancer could tip the scales towards early diagnosis and catch the cancer at a point when it is still curable.

How is the Peer Reviewed Cancer Research Program (PRCRP) Addressing This Global Problem?

The liver cancer topic area for the PRCRP was included in the congressional language of the Department of Defense appropriation starting in fiscal year 2015 (FY15). Since then, $13,386,550 has been invested in 31 research grants. The projects funded by the PRCRP are aimed at addressing critical research gaps within the field of liver cancer, as well as unresolved questions, using both basic science and clinical research techniques. Below are just a few of the questions being addressed by PRCRP-funded investigators:

How can we identify individuals at risk of developing liver cancer?

Dr. Yujin Hoshida, Icahn School of Medicine at Mount Sinai

In the United States, infection with hepatitis C virus (HCV) is the leading cause of HCC and accounts for 40% of cases.5Dr. Yujin Hoshida, with an FY15 Idea Award with Special Focus, will describe the molecular changes that are maintained within liver cells long after the clearance of HCV infection, but prior to the establishment of liver cancer. This work will help create a gene-based diagnostic platform to identify patients at risk of developing liver cancer due to past HCV exposure.

How can we more effectively classify the different stages of liver cancer progression?

From left to right: Dr. Hao Zhu, Dr. Adam Yopp, Dr. Amit Singal, and Dr. Daniel Siegwart, University of Texas Southwestern Medical Center, Dr. Akbar Waljee, University of Michigan

The system currently used for diagnosing, describing, and monitoring the stage of liver cancer relies on imaging data to assess whether the cancer has spread within the organ or to other parts of the body and does not account for other biological changes that occur within the cancer cells.4 Drs. Hao Zhu, Adam Yopp, Amit Singal, and Daniel Siegwart of the University of Texas Southwestern Medical Center at Dallas and Dr. Akbar Waljee of the University of Michigan received an FY15 Translational Team Science Award to characterize patient-derived xenografts at various disease stages. From this work, they hope to establish a more refined staging procedure, based on the molecular signature of HCC cells, and also identify prognostic biomarkers that predict patient sensitivity to therapy.

Why are men diagnosed with liver cancer at a higher rate than women?

Dr. Yun-Fai Lau, Northern California Institute for Research and Education

According to the latest data from the National Cancer Institutes’ Surveillance, Epidemiology, and End Results (SEER) Program, men are three times more likely to be diagnosed with liver cancer than women.2 With an FY15 Idea Award with Special Focus, Dr. Yun-Fai Lau aims to validate a male-specific cancer gene, TSPY, as a diagnostic and predictive marker in liver cancer. This work may help explain the sex-specific disparity in liver cancer risk and establish how TSPY and other Y chromosome-expressed genes contribute to liver cancer pathology in men.

Moving Forward, Much More Still Needs to be Done

Each year, the PRCRP consults with researchers, clinicians, advocates, and survivors to develop a targeted investment strategy that aims to fill critical knowledge and resource gaps within liver cancer research. By acknowledging these gaps, the PRCRP can promote impactful research to improve prevention, detection, treatment, and survivorship. Furthermore, by addressing these gaps, advances can be made to help improve the health and well-being of affected individuals, including Service members, their families, and the American public.

Publications:

  1. Cancer Fact Sheet. World Health Organization (http://www.who.int/mediacentre/factsheets/fs297/en/).
  2. SEER Cancer Stat Facts: Liver and Intrahepatic Bile Duct Cancer. National Cancer Institute. Bethesda, MD (http://seer.cancer.gov/statfacts/html/livibd.html).
  3. Liver Cancer. Centers for Disease Control and Prevention. Atlanta, GA (https://www.cdc.gov/cancer/liver/index.htm).
  4. Adult Primary Liver Cancer Treatment (PDQ®)–Health Professional Version. National Cancer Institute, Bethesda, MD (https://www.cancer.gov/types/liver/hp/adult-liver-treatment-pdq).
  5. McMahon B, Block J, Block T, Cohen C, Evans AA, Hosangadi A, London WT, Sherman M, on behalf of the 2015 Princeton HCC Workshop Participants. 2016. Hepatitis-associated liver cancer: gaps and opportunities to improve care. Journal of the National Cancer Institute 108(4):djv359 (https://doi.org/10.1093/jnci/djv359).

Links:

Public and Technical Abstracts: Gene Regulatory Networks as Targets and Biomarkers for Liver Cancer Chemoprevention After Clearance of Oncogenic Hepatitis C Virus
Public and Technical Abstracts: Defining Hepatocellular Carcinoma Subtypes and Treatment Responses in Patient-Derived Tumorgrafts
Public and Technical Abstracts: The Genetic Basis of Sex Differences in Liver Cancer

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Last updated Wednesday, October 18, 2017