Drugs that enhance levels of small molecules derived naturally in the body from a major component of animal fats (small molecules known as epoxyeicosatrienoic acids [EETs]) are currently in clinical trials for the treatment of high blood pressure and diabetes. A team of researchers — led by Dipak Panigrahy and Mark Kieran, at the Dana-Farber Cancer Institute, Boston; Sui Huang, at the Institute for Systems Biology, Seattle; and Darryl Zeldin, at the National Institute of Environmental Health Science, Research Triangle Park — has now generated data in mice that raise concern about the use of these drugs in humans.
The key observation of the team was that EETs promote primary tumor growth and spread to distant sites (metastasis) in a variety of mouse models of cancer. As noted by the authors and, in an accompanying commentary, Raymond DuBois and Dingzhi Wang, at The University of Texas MD Anderson Cancer Center, Houston, the data generated suggest not only that raising levels of EETs in humans could have severe adverse effects but also that EET antagonists could provide a new approach to preventing and treating metastasis.
TITLE: Epoxyeicosanoids stimulate multiorgan metastasis and tumor dormancy escape in mice
AUTHOR CONTACT:
Sui Huang
Institute for Systems Biology, Seattle, Washington, USA.
Phone: 206-354-3569; Fax: 206-732-1299; E-mail:
sui.huang@systemsbiology.org .
Mark W. Kieran
Dana-Farber Cancer Institute, Harvard Medical School, Boston,
Massachusetts, USA.
Phone: 617-632-4907; Fax: 617-632-4897; E-mail:
mark_kieran@dfci.harvard.edu .
Darryl C. Zeldin
National Institute of Environmental Health Science, NIH, Research
Triangle Park, North Carolina, USA.
Phone: 919-541-1169; Fax: 919-541-4214; E-mail:
zeldin@niehs.nih.gov .
ACCOMPANYING COMMENTARY
TITLE: Epoxyeicosatrienoic acids: a double-edged sword in cardiovascular diseases and cancer
Journal of Clinical Investigation