Liver cancer is the fifth most common cancer in men and the ninth most common cancer in women worldwide. The incidence rate of liver cancer is larger in developing countries, but is, unfortunately, rapidly growing in the U.S.
- An estimated 42,810 new cases of liver cancer will be diagnosed in the U.S. in 2020, with 30,160 deaths expected to result from the diagnosis.
- For the 44% of people who are diagnosed with liver cancer at localized-stage, the five-year survival rate is 33%.
- For those people diagnosed with liver cancer at regional stages, the five-year survival rate drops to 11%.
- In the U.S., liver cancer incidence has more than tripled since 1980.
- Liver cancer is three times as likely to occur in men than in women.
- The liver is a common place where cancer spreads. Colorectal, breast and lung cancers are the most common sources of cancer that metastasize to the liver.
- Approximately 70% of liver cancer cases in the US could potentially be prevented through elimination of risk factors, the most important include: excess body weight; type 2 diabetes; infection with hepatitis B virus (HBV) and/or hepatitis C (HCV), heavy alcohol consumption and tobacco smoking.
Source: American Cancer Society’s Cancer Facts & Figures 2020 and GLOBOCAN, 2018
Liver Cancer Research
In addition to specific projects listed below, genomics research is helping us attack liver cancer – and all types of cancer. NFCR has distinguished itself from other organizations by emphasizing long-term, transformative research and working to move people toward cancer genomics.
With NFCR funding since 1991, Dr. Yung-Chi Cheng and his team developed YIV-906, a botanical drug that enhances anti-cancer activity in immunotherapy, chemotherapy and radiotherapy. YIV-906 also reduces the unpleasant gastrointestinal side effects of chemotherapy. Patients with colon and rectal cancers were some of the first patients to experience these beneficial properties of YIV-906 in early Phase I clinical trials.
With support from the NFCR AIM-HI Translational Research Initiative, Dr. Cheng has now brought YIV-906 to a global Phase II clinical trial in 2020. YIV-906 is first treating Hepatitis B Virus (HBV)-associated liver cancer patients in combination with sorafenib, a front-line drug that has modest response rates and serious toxicities. If YIV-906 improves patients’ outcomes, it could become one of the first FDA-approved oral herbal medicines for anti-cancer treatment. Its acceptance as an approved drug would facilitate future clinical trials to benefit patients with other types of cancer. Significantly, since YIV-906 affects multiple biological systems, it will usher in a new model for drug discovery to treat patients holistically.
One of the major signaling proteins in tumor formation and suppression of our immune system found in over 50% of cancers is STAT3. As an activator of gene expression, STAT3 controls networks of genes that allow cancer growth and metastasis (spreading). However, the development of a drug that targets STAT3 has been a challenge for the research community, earning STAT3 the label of ‘undruggable’.
Dr. Ron DePinho and his colleagues used computer-based drug screening of hundreds of thousands of compounds from chemical libraries to identify several compounds that inhibit STAT3 protein in complex tumor models of various cancers. With funds from the NFCR AIM-HI Translational Research Initiative, the scientists have brought the lead inhibitor agent to a Phase I clinical trial to treat liver and other advanced cancers, giving patients hope that their lives may be saved.
Dr. Paul Fisher discovered MDA-9/ Syntenin, a gene that promotes the deadly spread (metastasis) of many cancers. With Dr. Web Cavenee, they discovered an innovative drug called PDZ1i to block the gene’s early signals that lead to cancer spreading. PDZ1i enhances the effects of radiation and the frontline liver cancer drug, sorafenib. PDZ1i has promise to significantly improve survival of liver cancer patients. The scientists are translating their research on PDZi treatment to benefit liver cancer patients in a future clinical trial with support from the NFCR AIM-HI Translational Research Initiative.
Cytokine IL/24, or an immune modulator gene also discovered by Dr. Fisher, locates and destroys primary and metastatic tumor cells throughout the body but is non-toxic to healthy cells. IL/24 also activates our immune system, inhibits new blood vessel formation to starve tumors of blood and nutrients, and sensitizes tumor cells to radiation, chemotherapy and immunotherapy. Dr. Fisher is developing different approaches for IL/24 gene therapy for liver and other types of cancer including a theranostic approach (detection combined with treatment and monitoring) and an adoptive cell therapy that supercharges patient’s immune T cells with IL/24 gene.
With funding from the NFCR AIM HI Translational Research Initiative, Dr. Fisher and Dr. Web Cavenee are advancing IL/24 gene therapy to a phase I clinical trial first for aggressive brain cancer, GBM. They hope to advance the IL/24 treatment for liver and other cancers so many patients can benefit from this powerful gene therapy.