Nearly everyone has had their life touched by cancer, the more than 100 diseases that have in common uncontrolled cell growth of DNA damaged cells. 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, the discovery of new medicines that selectively target cancer cells is still urgently needed.
A primary mission for the Marine Biomedical and Biotechnology Research Program (MBBRP) is to discover marine natural products with utility as medicines or as tools to allow us to better understand the molecular basis of disease. 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. 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. Some compounds are under evaluation by pharmaceutical companies for their potential use as drugs.
Our current focus is to look for treatments for pancreatic cancer, the fourth leading cause of cancer death in the US. To achieve this, we are looking beyond compounds that directly kill cancer cells to compounds that can change 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
NIH R21CA176222-01 (Guzmán). “Targeting RAGE in pancreatic cancer.” 03/19/13-02/28/15. 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.
HBOI/FAU Postdoctoral Program (Guzmán). Identification of Novel Inhibitors of Inflammation to be used as Chemo-preventatives of Pancreatic Cancer. 09/27/10 -09/26/12. This award provided funds to hire a postdoctoral investigator to assist me in my studies to identify novel inhibitors of inflammation that have the potential to prevent the initiation of pancreatic cancer.
NIH R03CA141199-01 (Guzmán). “Identification of bioactive marine natural products that inhibit mast cells implicated in pancreatic cancer etiology.” 07/01/09-06/30/12. The overall objective of the proposed research project is to identify bioactive marine natural products that inhibit mast cell migration and degranulation as potential novel chemo-preventatives of pancreatic cancer.
09BN-08-23088 (Guzmán). “Discovery of Novel Anti-inflammatory Compounds for Use as Chemopreventatives of Pancreatic Cancer.” 7/1/09-12/30/12. The major goals of this project are to identify novel inhibitors of the signaling pathways NFκB, IL-8 and STAT3, important in inflammation and pancreatic cancer initiation and progression, among the HBOI library of marine natural compounds and to validate the activity of those samples through secondary assays.