A Journey Towards Cancer Drug Discovery

Among the various drugs that are used for the treatment of human sufferings anticancer drugs may receive the distinction of being the most toxic to the human body. The side effects and toxicities of the anticancer drugs are primarily due to their inability to differentiate between the cancer cells and the normal cells in the body such as bone marrow cells and epithelial cells that are actively dividing. Some of the modern approaches are geared towards developing drugs or drug combination that are less toxic to the body and more effective towards cancer cells and tissues. In the process of effectively treating a cancer growth availability of sensitive methods for diagnosis also play a major role. The cancer research at the NSU (Nova Southeastern University) College of Pharmacy is focused on developing both therapeutics as well as sensitive diagnostic methods. One of the processes we have been targeting for the purpose of stopping the cancer growth and metastatic spread of cancer is known as angiogenesis, an intra tumoral process that helps the tumor to grow beyond 1 mm3 – 1 cm3 in size. Completion of angiogensis results in the formation of new blood vessels that traverse the tumor tissues and nourish them by providing oxygen and nutrients through establishment of blood circulation. Various growth factors, hormones and cytokines are known to be involved in the regulation of angiogenesis, however, the most important growth factor that controls angiogenesis is known as Vascular Endothelial Growth Factor (VEGF). Proangiogenic action of VEGF is mediated through VEGF receptors (VEGFR) and by the activation of associated kinases. For the purpose of inhibiting the angiogenic process several inhibitors of VEGF and VEGFR have been developed and one of them is a monoclonal antibody drug commercially available as Bevacizumab®. For the purpose of developing much stronger and highly specific angiogensis inhibitors we utilized molecular modeling approaches in collaboration with scientists from the Lombardi Comprehensive Cancer Center at Georgetown University. Through molecular modeling approach we were able to discover two drug molecules along with several others from a collection of molecules that exceeded 1 million in number. Two compounds, code named F16 and JFD, ranked at the top compared to several others that were identified through initial computer screening. Both these compounds showed strong cytotoxic as well as anti-angiogenic effects in our in vitro assays. The anti-tumor activity of these compounds was confirmed using the in vivo experiments also. Subsequently, patent applications were filed from NSU for the anti-tumor use of these compounds through their anti-angiogenic effect. The patent application for F16 was completed in 2006 and it is nearing approval at this time. The JFD patent application from NSU was completed in 2007 and is expected to be approved in 2009 Grants. This project was supported by the Center of Excellence for Marine Biology and Biotechnology grant from the state of Florida through FAU, also by the PFRD grant from NSU