According to the American Cancer Society, one out of every three Americans will have some form of cancer during their lifetime. While new treatments and early detection have improved the odds of survival for some cancers, the discovery of new medicines that selectively target cancer cells is still urgently needed.
A primary mission of the Marine Biomedical and Biotechnology Research Program (MBBR) is to discover marine natural products with utility as medicines or tools to allow us to better understand the molecular basis of dreaded diseases. This effort has identified over 100 natural products with cancer-fighting properties. Discodermolide, leiodermatolide, aphrocallistin, dictyostatin and neopeltolide block cells from dividing. Manzamine A reduces the invasiveness and resistance to programmed cell death (apoptosis) of pancreatic cancer cells through its effects on vATPases. Manzamine A also inhibits autophagy, a process by which cancer cells get nutrients and that may help them escape chemotherapies. Microsclerodermin A and spongiatriol target NFκB, an important mediator of inflammation which has a strong link with cancer. Some of our compounds prevent mast cells — immune cells that in pancreatic cancer appear to facilitate the initiation and progression of the disease— from degranulating, and thus releasing the growth and blood-vessel-forming factors contained within them.
Our current focus is to look for treatments for pancreatic cancer, the fourth-leading cause of cancer death in the United States. To achieve this, we are looking beyond compounds that directly kill cancer cells to compounds that can change the signaling inside the cancer cell or the tumor microenvironment that facilitates tumor initiation and progression, as well as compounds that can enhance or restore the immune response against the tumor. A future focus is to find compounds that target cancer stem cells, which are responsible for the recurrence of tumors after a patient is thought to be cured.
Our research was highlighted in an episode of the Miami PBS Series Changing Seas titled “Prescription: Oceans.” Watch the episode
7BC06 (Wright). Discovery of Marine Natural Products Antagonists of Survivin as Novel Cancer Therapeutics. 3/1/2017-2/28/2020. This project seeks to screen a structurally diverse library of marine natural products to identify inhibitors of survivin that can contribute to our understanding of this important protein and their utility in the treatment of cancer.
HBOIF Save Our Seas License Plate Pilot Project (Guzmán). Development of a 3D spheroid breast cancer cell assay for screening peak library fractions from organisms collected in Florida waters. 7/1/2016-6/30/2017. The major goal of this project is to set up a 3D spheroid breast cancer cell assay to identify compounds with utility against this disease from the HBOI libraries of marine natural compounds and peak library.
HBOIF (Guzmán). Transforming Natural Products Discovery: Cancer Immunology. 03/23/15-03/22/17. The major goal of this project is to set up phenotypical cell-based assays to identify modulators of the immune response from the HBOI libraries of marine natural compounds and peak library.
NA09OAR4320073 (Pomponi) NOAA Cooperative Institute for Ocean Exploration, Research and Technology Project # 4.3.1 (Wright) Discovery of Novel Therapeutic Agents from Marine Frontier Habitats. 07/01/09-06/30/17. The major goal of this project is to discover bioactive marine natural products that lead to novel chemotherapeutics for the treatment of many diseases.
NIH R21CA176222-01 (Guzmán). “Targeting RAGE in pancreatic cancer.” 03/19/13-02/28/16. This project seeks to initiate a screening effort for inhibitors of the receptor for advanced glycation end products (RAGE), an important regulator of inflammatory, stress and survival pathways, in pancreatic cancer cells using a unique library of marine natural products.
2013 FAU Seed Grant (Guzmán). Discovery of Marine Natural Products that Modify Tumor Cell Immune Evasion. 2/1/13-2/1/14. The major goal of this project is to develop and validate an assay that will identify materials that can restore levels of the Major Histocompatibility Complex I (MHC I) in pancreatic cancer cells.
NIH R01CA093455-06 (Wright). Discovery of Novel Compounds with Activity against Pancreatic Cancer. 7/01/10-6/30/13. The major goal of this project is to discover bioactive marine natural products that lead to novel chemotherapeutics for the treatment of pancreatic cancer.