Library Subscription: Guest
Begell Digital Portal Begell Digital Library eBooks Journals References & Proceedings Research Collections
Critical Reviews™ in Oncogenesis
SJR: 0.631 SNIP: 0.503 CiteScore™: 2

ISSN Print: 0893-9675
ISSN Online: 2162-6448

Critical Reviews™ in Oncogenesis

DOI: 10.1615/CritRevOncog.2013007921
pages 409-434

Iron Chelation: Inhibition of Key Signaling Pathways in the Induction of the Epithelial Mesenchymal Transition in Pancreatic Cancer and Other Tumors

Alexander Richardson
Iron Metabolism and Chelation Program, Department of Pathology and Bosch Institute, University of Sydney, Sydney, New South Wales, 2006, Australia
Zaklina Kovacevic
Iron Metabolism and Chelation Program, Department of Pathology and Bosch Institute, University of Sydney, Sydney, New South Wales, 2006, Australia
Des R. Richardson
Iron Metabolism and Chelation Program, Department of Pathology and Bosch Institute, University of Sydney, Sydney, New South Wales, 2006, Australia

ABSTRACT

Pancreatic cancer is the fourth leading cause of cancer-related deaths worldwide in both men and women. It presents late with non-specific symptoms, which makes it difficult to diagnose until the cancer has progressed and metastasized. Metastasis is facilitated by the epithelial-to-mes-enchymal transition (EMT), which is promoted via the oncogenic transforming growth factor beta (TGFβ), Wnt, and nuclear factor kappa B (NFκB) signaling pathways. However, recent studies have demonstrated that the EMT can be inhibited by novel anti-cancer agents known as thiosemicarbazone iron chelators. These novel agents also up-regulate the metastasis suppressor, N-myc downstream regulated gene 1 (NDRG1), which can restore normal signaling to the cell and suppresses metastasis via inhibition of the EMT. Through the ability of iron chelators to up-regulate NDRG1 expression and affect multiple molecular targets, these agents have the potential to maintain the epithelial phenotype of cancer cells and may lead to improved survival rates for patients with late-stage disease.