Identification of novel compounds that inhibit S100P and RAGE binding as a new therapy for pancreatic cancer

International Conference and Exhibition on Molecular Medicine and Diagnostics

August 24-26, 2015 London, UK

Louise S Mackenzie, Debbie Ogbeni, Ramatoulie Camara and Sharon Rossiter

Scientific Tracks Abstracts: J Mol Genet Med

Abstract :

Pancreatic adenocarcinoma (PDAC) is one of the most lethal human cancers with a 5-year survival of less than 5% due mostly
to the lack of effective therapy and difficulty of detection at an early stage of development. Recent studies have shown a high
prevalence of S100 proteins in PDAC, in particular the calcium-binding protein S100P. It has been proposed that the metastasispromoting
calcium-binding protein S100P which possesses both intracellular and extracellular functions activates key cell signaling
pathways, including MAP kinase and nuclear factor NFκB pathways through its extracellular interaction with the receptor for
advanced glycation end products (RAGE). The interaction between RAGE-S100P stimulates pancreatic tumor proliferation, survival,
invasion and metastasis progression in vitro and tumor metastasis in vivo. Using computational chemistry methods, our laboratory
have identified 87 novel compounds that prevent S100P binding to RAGE. Here in this talk we will outline the key challenges and
methodology used to validate an ELISA to measure S100P and RAGE interaction. Our initial results highlight 22 new lead compounds
that inhibit S100P-RAGE interaction, some of which have shown an ability to decrease pancreatic cell line growth. This work is
supported by the Association for International cancer research and the University of Hertfordshire.

Biography :

Louise S Mackenzie completed her PhD at Imperial College, London, and continued in Postdoctoral study at Imperial College and the William Harvey Research Institute.
Currently a Senior lecturer in Pharmacology at the University of Hertfordshire, she has published 22 full papers and 5 review articles in reputed journals.