Through our research, we aim to translate basic science and clinical observations into discoveries that would improve the prevention and treatment of GI cancers. Thus, our projects range from basic science to clinical trials.
Chemoprevention of Pancreatic Cancer. Pancreatic ductal adenocarcinoma (PDAC) remains the most lethal solid tumor and the fourth leading cause of cancer-related deaths in the US. One of the main reasons for this outcome includes the lack of effective prevention strategies. Currently there is no effective chemoprevention agent for pancreatic cancer and less than five agents have entered early phase clinical trials. Since consumption of fruits and vegetables has been associated with a reduced risk of pancreatic cancer, we have been interested in identifying and developing bioactive food components that might be effective against pancreatic cancer. To that end, we have discovered that Vitamin E δ-tocotrienol is the most effective vitamin E against pancreatic cancer. Furthermore, we have completed pre-clinical studies in highly relevant models of pancreatic ductal adenocarcinoma development and translated these findings to early phase trials. Currently, we are pursuing a placebo-controlled, randomized phase II trial to prevent pancreatic cancer relapse in subjects that have had curative resection of their pancreatic tumors.
Vitamin E signaling in cancer. Vitamin E has been of intense interest in oncology due to its free radical scavenging properties. Based on the concept that free radicals from cellular metabolism lead to DNA damage and thereby carcinogenesis, vitamin E had been investigated for its cancer protective effect. However, large scale randomized clinical trials have shown disappointing, and even occasional paradoxical effect of vitamin E chemoprevention of cancer. Emerging insights reveal that the class of vitamin E (tocopherols) which have been studied so far are not the most potent class of vitamin E anticancer compounds. Experimental evidence suggests that the other class of vitamin E (tocotrienols) have more potent anticancer properties. Furthermore, the anticancer properties of these compounds do not appear to be related to the antioxidant properties of vitamin E compounds. Therefore, there is an unmet scientific need to understand vitamin E signaling in cancer. We have demonstrated several unique signaling properties of tocotrienols in cancer. Currently, we are pursuing detailed mechanistic molecular studies to confirm tocotrienol cellular targets which we have identified from MicroArray, and non-coding RNA screenings. Understanding the molecular basis of the mechanism of action of bioactive vitamin E may not only uncover novel targets for cancer prevention and treatment but will also assist in the design of personalized chemoprevention trials with vitamin E.
Biomarkers in early detection and prognosis of pancreatic cancer. The highly lethal nature of pancreatic cancer, as well as recognition of high-risk individuals, has made research into early detection a high priority. We have embarked on the discovery of early detection biomarkers, such as microRNA signatures in pancreatic cancer. We have identified microRNA signatures and imaging features which can better discriminate high-risk cystic tumors of the pancreas. In addition, we have been studying molecular signatures that predict outcomes in early stage pancreatic cancer. To this end we have identified Annexin-A8 as a prognostic marker and potential therapeutic target for pancreatic cancer. We have also identified a 15 gene signature that is predictive of outcomes after surgical resection of pancreatic cancer. Currently, we are pursuing validation studies of these signatures in patients.
Chemoprevention of colorectal cancer. In the United States, colorectal cancer is the second leading cause of cancer deaths. Therefore, new strategies for prevention are needed to reduce the burden of this disease. Results from clinical trials and experimental data indicate that d-tocotrienol, an unsaturated natural form of vitamin E, is safe, and might have chemopreventive effects against cancer, including colon cancer. However, no clinical trial data exists for the use of vitamin E d-tocotrienol (VEDT) for colorectal cancer chemoprevention. Therefore, we are pursuing a double-blind, placebo-controlled, randomized trial to assess the safety and chemopreventive effects of VEDT on sporadic colon cancer (assessed by adenoma and polyp recurrence) in adult patients who previously had stage 0-III colorectal cancer resected by surgery. A total of 150 subjects will be randomly assigned (1:1) to receive oral VEDT (600 mg twice daily) or placebo tablets for 1 year prior to routinely scheduled surveillance colonoscopy. We are also pursuing preclinical studies of VEDT in colon cancer to better understand VEDT signaling in cancer and to generate new knowledge that might help with future clinical trial design.