Liver cancer remains one of the deadliest cancers and claims the lives of 1,645 people worldwide each day. Many are Asians with chronic hepatitis B. Early diagnosis is the best way to improve one's chances of surviving liver cancer, but the current screening blood test can miss 50 percent of the cancers. In fact, there is no effective chemotherapy to treat those who are diagnosed in the later stages of liver cancer. Although research and early detection has led to significant improvement in the prognosis of many cancers, liver cancer—which largely affects the Asian and African populations—has received little federal research funding.
The Asian Liver Center's comprehensive liver cancer research program is committed to finding a cure for liver cancer through novel approaches toward increasing the efficacy of diagnosis, prognosis, and treatment of liver cancer. The Asian Liver Center spearheaded studies that led to the publication in 2002-03 of the first major genomic analysis of liver and stomach cancers. These important studies have provided us with a rich foundation of information that will guide future research.
Publications By Year
Sukumaran, S., Tan, M., Ben-Uliel, S. F., Zhang, H., De Zotti, M., Chua, M. S., So, S. K., & Qvit, N. (2023). Rational design, synthesis and structural characterization of peptides and peptidomimetics to target Hsp90/Cdc37 interaction for treating hepatocellular carcinoma. Computational and Structural Biotechnology Journal, 21, 3159-3172.
Ahmad F, Ma L, Wei W, Liu Y, Hakim I, Daugherty A, Mujahid S, Radin AA, Chua MS, So S. Identification and validation of microtubule depolymerizing agent, CYT997, as a potential drug candidate for hepatocellular carcinoma. Liver Int. 2023 Oct 13. doi: 10.1111/liv.15756. Epub ahead of print. PMID: 37833852.
Lerner, Y., Sukumaran, S., Chua, M. S., So, S. K., & Qvit, N. (2022). Exploring Biomolecular Interaction Between the Molecular Chaperone Hsp90 and Its Client Protein Kinase Cdc37 using Field-Effect Biosensing Technology. Journal of Visualized Experiments, (181).
Shi, H., Huttad, L. V., Tan, M., Liu, H., Chua, M. S., Cheng, Z., & So, S. (2021). NIR-II imaging of hepatocellular carcinoma based on a humanized anti-GPC3 antibody. RSC Medicinal Chemistry, 13(1), 90-97.
Natarajan, A., Zhang, H., Ye, W., Huttad, L., Tan, M., Chua, M. S., Gambhir, S. S., & So, S. K. (2021). A Humanized Anti-GPC3 Antibody for Immuno-Positron Emission Tomography Imaging of Orthotopic Mouse Model of Patient-Derived Hepatocellular Carcinoma Xenografts. Cancers, 13(16), 3977.
Ren, Y., He, S., Huttad, L., Chua, M. S., So, S. K., Guo, Q., & Cheng, Z. (2020). An NIR-II/MR dual modal nanoprobe for liver cancer imaging. Nanoscale, 12(21), 11510-11517.
Gani, A. W., Wei, W., Shi, R. Z., Ng, E., Nguyen, M., Chua, M. S., So, S., & Wang, S. X. (2019). An Automated, Quantitative, and Multiplexed Assay Suitable for Point-of-Care Hepatitis B Virus Diagnostics. Scientific Reports, 9(1), 15615.
Kim, H., Fuchs, G., Wang, S., Wei, W., Zhang, Y., Park, H., Roy-Chaudhuri, B., Li, P., Xu, J., Chu, K., Zhang, F., Chua, M., So, S., Zhang, C., Sarnow, P., and Kay, M. A. (2018). "A transfer RNA derived small RNA affects translation in rapidly dividing cells and a target for hepatocellular carcinoma." AMER ASSOC CANCER RESEARCH.
Chen, B., Wei, W., Ma, L., Yang, B., Gill, R. M., Chua, M., Butte, A. J., and So, S. (2017). "Computational Discovery of Niclosamide Ethanolamine, a Repurposed Drug Candidate That Reduces Growth of Hepatocellular Carcinoma Cells In Vitro and in Mice by Inhibiting Cell Division Cycle 37 Signaling." Gastroenterology, 152(8), 2022-2036.
Chen, B., Ma, L., Paik, H., Sirota, M., Wei, W., Chua, M. S., So, S., & Butte, A. J. (2017). Reversal of cancer gene expression correlates with drug efficacy and reveals therapeutic targets. Nature Communications, 8, 16022. doi: 10.1038/ncomms16022.
Kim, H. K., Fuchs, G., Wang, S., Wei, W., Zhang, Y., Park, H., ... Kay, M. A. (2017). A transfer-RNA-derived small RNA regulates ribosome biogenesis. Nature, 552(7683), 57-62.
Song, C. X., Yin, S., Ma, L., Wheeler, A., Chen, Y., Zhang, Y., ... Quake, S. R. (2017). 5-Hydroxymethylcytosine signatures in cell-free DNA provide information about tumor types and stages. Cell Research, 27(10), 1231-1242.
Cholankeril, G., Perumpail, R. B., Hu, M., Pham, E. A., Kumari, R., Gish, R., So, S. K., Dhanasekaran, R., and Ahmed, A. (2016). "Differences in Hepatocellular Carcinoma Incidence and Survival Rates among Asian Mono-Ethnicities." WILEY, 860A.
Perumpail, R. B., Ahmed, A., Higgins, J. P., So, S. K., Cochran, J. L., Drobeniuc, J., Mixson-Hayden, T. R., and Teo, C. (2015). "Fatal Accelerated Cirrhosis after Imported HEV Genotype 4 Infection." Emerging Infectious Diseases, 21(9), 1679-1681.
Ma, L., Wang, X., Jia, T., Wei, W., Chua, M. S., & So, S. (2015). Tankyrase inhibitors attenuate WNT/β-catenin signaling and inhibit growth of hepatocellular carcinoma cells. Oncotarget, 6(28), 25390-401.
Lu, W. J., Chua, M. S., & So, S. K. (2015). Suppression of ATAD2 inhibits hepatocellular carcinoma progression through activation of p53- and p38-mediated apoptotic signaling. Oncotarget, 6(39), 41722-35.
Wang, Z., Wei, W., Sun, C. K., Chua, M. S., & So, S. (2015). Suppressing the CDC37 cochaperone in hepatocellular carcinoma cells inhibits cell cycle progression and cell growth. Liver International, 35(4), 1403-15.
Lu, W. J., Chua, M. S., Wei, W., & So, S. K. (2015). NDRG1 promotes growth of hepatocellular carcinoma cells by directly interacting with GSK-3β and Nur77 to prevent β-catenin degradation. Oncotarget, 6(30), 29847-59.
Yang, X., Liu, H., Sun, C. K., Natarajan, A., Hu, X., Wang, X., Allegretta, M., Guttmann, R. D., Gambhir, S. S., Chua, M., Cheng, Z., and So, S. K. (2014). Imaging of hepatocellular carcinoma patient-derived xenografts using Zr-89-labeled anti-glypican-3 monoclonal antibody. Biomaterials, 35(25), 6964-6971.
Ma, L., Wei, W., Chua, M., and So, S. (2014). Wnt pathway activation in hepatocellular carcinoma: A clinical perspective. Gastrointestinal Cancer: Targets and Therapy, 4, 49-63.
Ma, L., Chua, M. S., Andrisani, O., & So, S. (2014). Epigenetics in hepatocellular carcinoma: an update and future therapy perspectives. World Journal of Gastroenterology, 20(2), 333-45.
Wei, W., Wu, S., Wang, X., Sun, C. K., Yang, X., Yan, X., ... So, S. (2014). Novel celastrol derivatives inhibit the growth of hepatocellular carcinoma patient-derived xenografts. Oncotarget, 5(14), 5819-31.
Lu, W. J., Chua, M. S., & So, S. K. (2014). Suppressing N-Myc downstream regulated gene 1 reactivates senescence signaling and inhibits tumor growth in hepatocellular carcinoma. Carcinogenesis, 35(4), 915-22.
Zhao, P., Yang, X., Qi, S., Liu, H., Jiang, H., Hoppmann, S., ... Cheng, Z. (2013). Molecular imaging of hepatocellular carcinoma xenografts with epidermal growth factor receptor targeted affibody probes. Biomed Research International, 2013, 759057.
Chung, J. L., Pollack, J., Chua, M., So, S., Lin, C., and Lin, A. Y. (2012). Identification of a 14-gene signature that predicts survival in colorectal cancer with liver metastasis. 48th Annual Meeting of the American Society of Clinical Oncology (ASCO). AMER SOC CLINICAL ONCOLOGY.
Wang, Z., Wei, W., Sun, K., Chua, M., and So, S. (2012). Molecular effects of suppressing the CDC37 co-chaperone in hepatocellular carcinoma inhibit cell cycle progression and cell growth. 47th Annual Meeting of the European Association for the Study of the Liver (EASL). ELSEVIER SCIENCE BV, S130-S130.
Willingham, S. B., Volkmer, J. P., Gentles, A. J., Sahoo, D., Dalerba, P., Mitra, S. S., ... Weissman, I. L. (2012). The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors. Proceedings of the National Academy of Sciences of the United States of America, 109(17), 6662-6667.
Bu, L., Xie, J., Chen, K., Huang, J., Aguilar, Z. P., Wang, A., ... Chen, X. (2012). Assessment and comparison of magnetic nanoparticles as MRI contrast agents in a rodent model of human hepatocellular carcinoma. Contrast Media & Molecular Imaging, 7(4), 363-372.
Zhao, P., Yang, X., Qi, S., Cao, Q., Chua, M., Wang, J., So, S., and Cheng, Z. (2011). Optical imaging of liver carcinoma xenografts using epidermal growth factor receptor targeted fluorescently labeled affibody. 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD). WILEY-BLACKWELL, 894A-894A.
Darpolor, M. M., Yen, Y., Chua, M., Xing, L., Clarke-Katzenberg, R. H., Shi, W., Mayer, D., Josan, S., Hurd, R. E., Pfefferbaum, A., Senadheera, L., So, S., Hofmann, L. V., Glazer, G. M., and Spielman, D. M. (2011). In vivo MRSI of hyperpolarized [1-^13C]pyruvate metabolism in rat hepatocellular carcinoma. NMR in Biomedicine, 24(5), 506-513.
Hutton, D. W., Brandeau, M. L., and So, S. K. (2011). Doing Good with Good OR: Supporting Cost-Effective Hepatitis B Interventions. Interfaces, 41(3), 289-300.
Wei, W., Chua, M. S., Grepper, S., & So, S. (2011). Soluble Frizzled-7 receptor inhibits Wnt signaling and sensitizes hepatocellular carcinoma cells towards doxorubicin. Molecular Cancer, 10, 16.
Sun, C. K., Chua, M. S., He, J., & So, S. (2011). Suppression of glypican 3 inhibits growth of hepatocellular carcinoma cells through up-regulation of TGF-β2. Neoplasia, 13(8), 735-747.
Lin, A. Y., Chua, M. S., Choi, Y. L., Yeh, W., Kim, Y. H., Azzi, R., ... Pollack, J. R. (2011). Comparative profiling of primary colorectal carcinomas and liver metastases identifies LEF1 as a prognostic biomarker. PLoS One, 6(2), e16636.
Wei, W., Chua, M. S., Grepper, S., & So, S. (2010). Small molecule antagonists of Tcf4/beta-catenin complex inhibit the growth of HCC cells in vitro and in vivo. International Journal of Cancer, 126(10), 2426-2436.
Wei, W., Chua, M. S., Grepper, S., & So, S. (2009). Blockade of Wnt-1 signaling leads to anti-tumor effects in hepatocellular carcinoma cells. Molecular Cancer, 8, 76.
Lin, A. Y., Fisher, G. A., So, S., Tang, C., Levitt, L. (2008). Phase H study of imatinib in unresectable hepatocellular carcinoma. American Journal of Clinical Oncology-Cancer Clinical Trials, 31(1), 84-88.
Sun, H., Chua, M., Yang, D., Tsalenko, A., Peter, B. J., So, S. (2008). Antibody Arrays Identify Potential Diagnostic Markers of Hepatocellular Carcinoma. Biomarker insights, 3, 1-18.
Yan, X., Chua, M. S., Sun, H., & So, S. (2008). N-Myc down-regulated gene 1 mediates proliferation, invasion, and apoptosis of hepatocellular carcinoma cells. Cancer Letters, 262(1), 133-142.
Yan, X., Chua, M. S., He, J., & So, S. (2008). Small interfering RNA targeting CDC25B inhibits liver tumor growth in vitro and in vivo. Molecular Cancer, 7, 19.
Rose, M. G., Yen, Y., So, S., Saif, M. W., Chu, E., Liu, S., Jiang, Z., Foo, A., Tilton, R., Cheng, Y. (2007). "Phase I/II study of PHY906/capecitabine in hepatocellular carcinoma." American Society of Clinical Oncology.
Chua, M. S., Sun, H., Cheung, S. T., Mason, V., Higgins, J., Ross, D. T., Fan, S. T., & So, S. (2007). Overexpression of NDRG1 is an indicator of poor prognosis in hepatocellular carcinoma. Modern Pathology, 20(1), 76-83.
Leung, S. Y., Ho, C., Tu, I., Li, R., So, S., Chu, K., Yuen, S. T., Chen, X. (2006). "Comprehensive analysis of 19q12 amplicon in human gastric cancers." Modern Pathology, 19(6), 854-863.
Liu, S., Foo, A., Jiang, Z., Marathe, R., Guan, J., Su, T., Tilton, R., Yen, Y., Rose, M., So, S., Chu, E., Cheng, Y. (2006). "PHY906 as a broad-spectrum enhancer in cancer therapy: Clinical and preclinical results in hepatocellular carcinoma." American Association for Cancer Research.
Aggarwal, A., Guo, D. L., Hoshida, Y., Yuen, S. T., Chu, K. M., So, S., Boussioutas, A., Chen, X., Bowtell, D., Aburatani, H., Leung, S. Y., Tan, P. (2006). "Topological and functional discovery in a gene coexpression meta-network of gastric cancer." Cancer Research, 66(1), 232-241.
Fong, C. W., Chua, M. S., McKie, A. B., Ling, S. H., Mason, V., Li, R., Yusoff, P., Lo, T. L., Leung, H. Y., So, S. K., & Guy, G. R. (2006). Sprouty 2, an inhibitor of mitogen-activated protein kinase signaling, is down-regulated in hepatocellular carcinoma. Cancer Research, 66(4), 2048-2058.
Chua, M. S., Bernstein, L. R., Li, R., & So, S. K. (2006). Gallium maltolate is a promising chemotherapeutic agent for the treatment of hepatocellular carcinoma. Anticancer Research, 26(3A), 1739-1743.
Patil, M. A., Gutgemann, I., Zhang, J., Ho, C., Cheung, S. T., Ginzinger, D., Li, R., Dykema, K. J., So, S., Fan, S. T., Kakar, S., Furge, K. A., Buttner, R., Chen, X. (2005). "Array-based comparative genomic hybridization reveals recurrent chromosomal aberrations and Jab1 as a potential target for 8q gain in hepatocellular carcinoma." Carcinogenesis, 26(12), 2050-2057.
Patil, M. A., Chua, M. S., Pan, K. H., Lin, R., Lih, C. J., Cheung, S. T., Ho, C., Li, R., Fan, S. T., Cohen, S. N., Chen, X., & So, S. (2005). An integrated data analysis approach to characterize genes highly expressed in hepatocellular carcinoma. Oncogene, 24(23), 3737-3747.
Hsu, C. P., Razavi, M. K., So, S. K., Parachikov, I. H., Benaron, D. A. (2005). "Liver tumor gross margin identification and ablation monitoring during liver radiofrequency treatment." Journal of Vascular and Interventional Radiology, 16(11), 1473-1478.
Lin, A. Y., Fisher, G., So, S., Tang, C., Levitt, L. (2005). "A phase II study of imatinib mesylate (IM) in patients (pts) with unresectable hepatocellular carcinoma (HCC)." 41st Annual Meeting of the American-Society-of-Clinical-Oncology. American Society of Clinical Oncology, 363S–363S.
Li, V. S., Wong, C. W., Chan, T. L., Chan, A. S., Zhao, W., Chu, K. M., So, S., Chen, X., Yuen, S. T., Leung, S. Y. (2005). "Mutations of PIK3CA in gastric adenocarcinoma." BMC Cancer, 5.
Cheung, S. T., Ho, J. C., Leung, K. L., Chen, X., Fong, D. Y., So, S., Fan, S. T. (2005). "Transcript AA454543 is a novel prognostic marker for hepatocellular carcinoma after curative partial hepatectomy." Neoplasia, 7(2), 91-98.
Lin, A. Y., Brophy, N., Fisher, G. A., So, S., Biggs, C., Yock, T. I., Levitt, L. (2005). "Phase II study of thalidomide in patients with unresectable hepatocellular carcinoma." Cancer, 103(1), 119-125.
The Asian Liver Center focuses on cancer genomic research using cutting-edge gene chip technology to develop diagnostic, prognostic, and treatment tools for liver cancer. Gene chip technology, first pioneered at Stanford University, is capable of studying the expression of tens of thousands of genes simultaneously on a surface area equivalent to the size of a piece of chewing gum. Using this new technology, the genomic research team studies the gene expression of tissue samples gathered from various liver tumors. Correlating the gene expression profiles with the clinical outcomes of the cancer, such as patient survival and cancer recurrence, may lead to the discovery of new prognostic tests and treatments.
Our genomics research helped us to identify several genes that are expressed in high abundance in liver tumor but not in normal liver. These genes may play important biological functions in the various processes involved in the cause and progression of liver cancer, and therefore be potential therapeutic targets in liver cancer. Unraveling the functions of these potentially cancer-causing genes will not only aid in our understanding of the biology of liver cancer, but also provide us with insights into novel therapeutic strategies for the treatment of liver cancer
Investigational anti-tumor agents
There are a limited number of treatment options for patients with liver cancer. In particular, the currently available standard of care drug for advanced liver cancer patients is sorafenib, which only prolongs overall survival by an average of 3 months. Thus, another focus of our research program is on the identification of novel chemotherapeutic or biological agents that are more efficacious than sorafenib. We use a traditional drug discovery approach to design small molecules or peptide inhibitors of molecular targets identified through our genomics study, as well as computational drug repurposing approaches to identify FDA-approved drugs (for other disease indications) that may have novel uses in the treatment of liver cancer.
Biomarkers for liver cancer
One of the main obstacles in the effective treatment of liver cancer is the ability to diagnose the cancer while it is in its early stages. The current biomarker used for liver cancer diagnosis (alpha-feto protein) has low sensitivity and specificity, causing a high percentage of patients to remain undiagnosed until the disease is far advanced. An important focus of our research program is on improving early detection of the disease. We work with Stanford scientists as well as external collaborators in using state-of-the-art technologies to allow more accurate and sensitive detection of novel protein biomarkers of liver cancer, and to detect cell free DNA mutations and expression patterns in the blood of liver cancer patients.