Natural Products Research
The Lee Lab, led by Dr. Richard Lee, is focused on understanding natural products at a molecular level to develop effective, new anti-cancer treatments. Natural products have been an important source for drug discovery. A review of FDA approved anticancer therapies found that 41% of anticancer drugs approved between 1940-2010 were either natural or naturally derived. Commonly used chemotherapies originally derived from natural plants include paclitaxel, irinotecan, vincristine and etoposide. More recently, trabectidin (originally identified from a sea squirt extract) was approved by the FDA for treatment of soft tissue sarcoma in 2015. These successes demonstrate the importance of identifying the active compound and understanding the mechanisms of action in order to develop new potential therapies from natural products.
The Lee Lab is currently focused on research in three areas: mistletoe, mushrooms and a PDX biobank.
Mistletoe refers to hemiparasitic plants as part of the order Santalales, and Viscum album is within the family Santalacaeae - commonly referred to as European mistletoe. This plant has been used medicinally since the 1500’s by Paracelsus, and more recently, Europeans have utilized Viscum album extracts as a natural product medicine. Preclinical studies both in vitro and in vivo have indicated that mistletoe extracts (ME) have anticancer effects using a variety of cells line and animal models and exert growth-inhibitory effects on a variety of human tumor cell lines in vitro via the induction of apoptosis or necrotic cell death.
We are working to define the mechanistic underpinnings of ML elicited anti-tumor efficacy in HCC, especially identifying the molecular targets that dictate their anti-tumor activity would optimize their use in the treatment of patients with advanced HCC. Furthermore, we are identifying accurate pharmacodynamics biomarkers would allow for real-time monitoring of the target effect in patients on ML derived treatments and would be critical to ensure the success of future clinical trials of ML. This research will help build the foundation for the development of an entirely new class of drug-like molecules with the potential for broad use in the treatment of advanced cancers.
Mushrooms have been used for centuries as part of traditional Chinese medicine and are believed to possess medicinal benefits including anticancer effects. Current hypotheses of mushrooms extracts for cancer treatment indicate an immune-mediated mechanism while others propose a direct effect on cancer cells. PSK and AHCC are specific mushroom extracts from Japan shown to improve survival for cancer patients in multiple prospective placebo-controlled clinical trials of colon and gastric cancer. We are actively investigating both the direct cancer effects and the immunomodulatory properties of PSK and AHCC that account for its clinical benefit in colon cancer, hepatocellular carcinoma, and other cancers.
Liver Cancer Sample Biobank for Generating Patient-Derived Xenografts
The overall goal of this study is to generate a liver cancer biobank with the goal of identifying and accelerating the development of new diagnostic and prognostic markers, new cancer prevention and treatment strategies, and to identify new targets for pharmaceutical interventions. We aim to develop better ways to diagnose and treat liver cancers by performing in-depth genomic analysis, including global analysis of gene expression, gene mutation analysis, SNP analysis, and non-coding RNA analysis on both normal and malignant tissue from patients undergoing tumor debulking due to the development of liver cancer.