Tumor In a Dish: Novel Approach for Personalized Medicine
Metastatic colorectal cancer is a major cause of cancer-related deaths. Most patients with metastatic disease fail to respond to chemotherapeutic agents. Hence, there is a dire need for developing new therapeutic and preventive agents that can target metastatic disease. Unfortunately, there are no good in vivo models available for studying metastatic disease, and current in vitro systems do not lend to studying metastasis either. Hence, in this abstract, we demonstrate the development of a new model, called “Tumor in a Dish” or TiD. In the multi-cell type TiD system, cancer cells were grown in a 3-dimensional (3D) culture containing normal epithelial cells, fibroblasts and endothelial cells. The model resembles in vivo tumor microenvironments, including cell-cell contact, tumor architecture, and the influence of different cell types. We next determined the efficacy of standard colon cancer treatment agents. We observed differential activity of 5FU in TiD system when compared to standard 2D and 3D cultures. Another surprising result we found was with freshly resected patient samples. Without knowing the genetic characteristics of the cancer tissue, the TiD method was able to identify cells that were resistant to oxaliplatin. Moreover, using this method, we have developed novel drugs that target cancer cells while not affecting the normal tissue. We have developed a novel method for identifying the appropriate therapeutic agent that specifically target tumor tissues. More importantly, the technique has significant utility in precision/personalized medicine, wherein this phenotypic screen can be coupled with current DNA pharmacogenetics to identify the ideal therapeutic agent, thereby increasing the probability of response to treatment while reducing unnecessary side effects.
Shrikant Anant, PhD
Shrikant Anant is currently the Tom and Teresa Walsh Professor of Cancer Prevention; Kansas Mason Professor of Cancer Research and the Vice Chair for Research in the Department of General Surgery at the University of Kansas Medical Center. He also served as the Associate Dean for Research at the Medical Center from July 2010 to December 2015. Dr. Anant earned his PhD. in Molecular Genetics from the University of Illinois (Chicago); M.S. in Microbiology from Michigan State University (East Lansing); MSc. in Medical Microbiology from the University of Madras (India), and his B.Sc. in Zoology with a Minor in Plant Biology & Chemistry from the University of Madras (India).
Prior to joining the KU Family, Dr. Anant wore many hats at the University of Oklahoma Health Sciences Center (Jan. 2008 through July 2010) serving as Associate Professor and then Professor of Medicine with Tenure, Professor of Cell Biology with Tenure & Graduate Faculty; Director of Gastroenterology Research Adjunct Professor of Pharmaceutical Sciences Department of Medicine/Gastroenterology and Nutrition; and Program Leader of Gastrointestinal Cancers.
While at the Washington University School of Medicine, St. Louis Mo, (Sept. 1998 through June 2006), Dr. Anant was a Research Assistant Professor and subsequently n Assistant Professor of Medicine in the Department of Internal Medicine, Division of Gastroenterology; Assistant Professor of Molecular Biology and Pharmacology; and Faculty Member of the Graduate Programs in Molecular Cell Biology, Biochemistry and Molecular Microbiology and Microbial Pathogenesis, Division of Biological and Biomedical Sciences.
Translating Research into Clinical Practice in Hepatocellular Cancer
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality and continues to increase in its incidence. The current standard of care for patients with HCC only provides limited therapeutic benefit. Development of innovative strategies is urgently needed. Experience with immunotherapy in HCC is quite early, but has rapidly progressed in the past 10 years. Multifaceted immune-based approaches have shown efficacy in achieving disease regression, representing the most promising new treatment approach in a number of malignancies, and we hope to extend these benefits to patients with HCC. To this end, we established a clinically relevant animal model by intraperitoneal injection of carbon tetrachloride and intrasplenic inoculation of potential oncogenic hepatocytes. As a result, tumors arise and grow in the setting of hepatic fibrosis. The established model mimics human HCC and reflects its typical features. Using this mode, we elucidated the complex dialog occurring between host immunity and tumors during tumor initiation and progression. We have leveraged these mechanistic findings to design clinically feasible antitumor therapeutic strategies. Four different strategies are in development by our team:
- Clinically feasible chemoimmunotherapy against HCC: Combination of sunitinib and anti-PD-1 antibodies for the treatment of HCC
- Integration of Liposome-loaded C6 ceramide and immunotherapy in the treatment of HCC
- Radiofrequency ablation in combination with sunitinib for the treatment of HCC
- Laser immunotherapy for the treatment of HCC
Kevin Staveley-O’Carroll, MD, PhD
Dr. Kevin Staveley-O’Carroll is a Professor of Surgery and Molecular Microbiology & Immunology at the University of Missouri School of Medicine (MU) and also serves as the Chair of Surgery and Director of the Ellis Fischel Cancer Center. Dr. Staveley-O’Carroll oversees the multidisciplinary clinical and basic science research programs in liver, pancreas, and gastrointestinal tumors. As a physician-scientist with these leadership roles, he is uniquely positioned to design, perform, and coordinate basic science research discovery, pre-clinical validation, and early clinical testing in patients.
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