The complex role of antioxidants in pancreatic cancer

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The complex role of antioxidants in pancreatic cancer

A paper published on July 6, 2011 in the prestigious journal Nature describes a novel role for antioxidants in pancreatic cancer. The lead author on this article is David Tuveson, MD, PhD, Chair of the Pancreatic Cancer Action Network Scientific Advisory Board, and recipient of a 2003 Pancreatic Cancer Action Network – AACR Career Development Award. Other contributors include Christine Iacobuzio-Donahue, MD, PhD (2007 Pancreatic Cancer Action Network Pilot Grant) and Ralph Hruban, MD (Scientific Advisory Board). Further, in the same issue of Nature, a summary of this study was co-written by Rushika Perera, PhD and Nabeel Bardeesy, PhD (2008 Randy Pausch, PhD – Pancreatic Cancer Action Network – AACR Pilot Grant).

In general, the role of antioxidants is to detoxify and block the formation of reactive oxygen species (ROSs). ROSs can be harmful to human cells, inducing DNA damage. This damage to DNA is characteristic of cancer cells, and promotes the formation and maintenance of tumors. For this reason, it has been believed that consumption of antioxidants in food or dietary supplements may play a role in preventing or alleviating cancer.

Contrary to previous reports implicating ROSs in causing or promoting cancer, this study by Dr. Tuveson and colleagues describes that cancer cells themselves have an inherent mechanism of reducing ROSs via antioxidants. This paper describes for the first time that the most commonly mutated protein in pancreatic cancer, K-Ras, can directly lead to expression of a protein called Nrf-2, stimulating an antioxidant cascade that reduces the levels of ROSs. Genetically blocking Nrf-2 leads to decreased growth and progression of pancreatic cancer cells in a mouse model of the disease, suggesting a potential therapeutic target.

Additional work will be necessary to understand the complex balance and activity of antioxidants and ROSs in human pancreatic cancer. It is also important to note that in addition to its role as an antioxidant, Nrf-2 leads to activation of a multitude of other behaviors in cancer cells. Therefore, a deeper understanding of the functions of K-Ras and Nrf-2 in pancreatic cancer will be critical.

Click here for the scientific abstract of this paper.
Click here for the news article describing this paper.

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