Current Cancer Drug Targets

Ruiwen Zhang 
Texas Tech University Health Sciences Center
1300 Coulter Drive
Amarillo, TX 79106
USA

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Role of the RAS in Pancreatic Cancer

Author(s): S. T. Lau, P. S. Leung.

Abstract:

Angiotensin II (Ang II), a main effector peptide of the renin-angiotensin system (RAS), mediates a hormonal action in the maintenance of blood pressure and electrolyte levels, and thus fluid homeostasis. Ang II also mediates paracrine, autocrine and/or intracrine actions in the control of various specific functions of diverse tissue organs. In the pancreas, Ang II exerts a growth promoting, angiogenic influence via the mediation of angiotensin II type 1 receptor (AT1R). Recent studies have implicated inappropriate activation of the local RAS in pancreatic cancer, including upregulation of AT1R and the angiotensin-converting enzyme (ACE), which consequently enhance Ang II-induced tumour activity. In addition to acting in a classical antihypertensive capacity, RAS blockers (AT1R blockers or ACE inhibitors) may yield protective effects against pancreatic cancer, a highly aggressive malignancy that is intrinsically resistant to radiotherapy and chemotherapy. Substantial experimental data from studies using cell and animal models of pancreatic cancer support the notion that RAS regulates tumour growth, angiogenesis, and metastasis; and a convergence of such findings suggests that pharmacological RAS blockade could have therapeutic potential in the management of pancreatic cancer. This review critically appraises the current research progress on the role of RAS in pancreatic cancer, and discusses the potential for developing drugs that target RAS for treatment of pancreatic cancer.

Keywords: Angiotensin II, angiotensin-converting enzyme inhibitor (ACEI), angiotensin II receotpr blocker (ARB), angiogenesis, cytotoxicity, pancreatic ductal adenocarcinoma (PDAC), pancreatic endocrine tumour, pancreatic ductal adenocarcinoma, vascular endothelial growth factor, Mas receptor, mitogen-activated protein kinase, angiotensinogen

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Article Details

VOLUME: 11
ISSUE: 4
Year: 2011
Page: [412 - 420]
Pages: 9
DOI: 10.2174/156800911795538110
Price: $58