Navigation Links
Targeting EETs to treat cardiovascular disease may prove a double-edged sword

Boston, Mass. A group of small molecules called EETs currently under scrutiny as possible treatment targets for a host of cardiovascular diseases may also drive the growth and spread of cancer, according to researchers at the Dana-Farber/Children's Hospital Cancer Center (DF/CHCC) and other institutions. Their findings also raise the possibility that drugs that block EETs could serve as a new avenue for cancer treatment.

This study, led by Dipak Panigrahy, MD, of DF/CHCC and the Vascular Biology Program at Children's Hospital Boston, appeared online December 19 in the Journal of Clinical Investigation.

EETs (or epoxyeicosatrienoic acids) are small fatty molecules, part of a larger family of lipids normally produced by the endothelial cells that line blood vessels to control inflammation and the response to injury. These molecules are also potent regulators of blood pressure, leading pharmaceutical companies to investigate compounds that raise EET levels for the treatment of nearly 20 cardiovascular diseases, including hypertension, stroke, and diabetes.

However, little work has been done to learn whether these molecules themselves might have some role to play in tumor growth or progression. This is despite evidence that enzymes that process EETs are associated with cancer, and that EETs can promote angiogenesis the growth of blood vessels.

"EETs have primarily been studied in models of cardiovascular disease," said the study's lead author, Dipak Panigrahy, MD. "This is the first time that direct administration of exogenous EETs and of specific EET antagonists has been investigated in pre-clinical cancer models."

In order to determine the extent of the relationship between EETs and cancer, Panigrahy and his collaborators conducted a series of studies using animal models of EET activity developed in the laboratory of Darryl Zeldin, MD, at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.

"NIEHS was pleased to work with such a distinguished international research team to address this important issue," Zeldin said.

With the models, the researchers were able to document that increasing the levels of EET levels either by increasing their natural production or injecting them systemically creates an environment conducive to tumor growth, even contributing to the transition of early tumors from a dormant state to active malignancy. They also found that EETs work in concert with VEGF, a potent stimulator of angiogenesis in both normal and cancerous tissues, to promote tumor metastasis, even in cancers that rarely spread to other organs.

"Many people have dormant tumors that may never become fully malignant," said Panigrahy. "The switch from a dormant to an active state is critically dependent on angiogenesis, as is metastasis, and so patients who have a high cancer risk could potentially increase that risk further by raising their EET levels."

The study team also found that compounds that block the activity of EETs, called EET antagonists, could reduce tumor growth and metastasis in the same animal models, suggesting that such compounds could have benefit as cancer treatments.

"Cardiovascular disease is a major cause of death in North America, and as such drugs that raise EET levels could provide significant benefit," says DF/CHCC's Mark Kieran, MD, PhD, one of the paper's senior authors. "We must be cautious, though, that in manipulating these molecules to regulate blood pressure we do not favor cancer growth and metastasis, another common cause of death.

"With these findings, though," Kieran continued, "we now have a better idea of how cancers drive themselves, opening up a new pathway for understanding and potentially treating cancer and metastasis that wasn't available to us before. At the same time, this data could potentially help inform the design of cardiovascular drugs that avoid raising cancer risk through this mechanism."


Contact: Children's Hospital Boston
Children's Hospital Boston

Related medicine news :

1. Tumor-targeting compound points the way to new personalized cancer treatments
2. Report Slams Makers of Sugary Drinks for Targeting Kids
3. Harvard Medical School and EPFL launch program targeting neurological disabilities
4. Could targeting a virus treat a common pediatric brain tumor?
5. New bone-targeting drug delays onset of metastases in hormone-resistant prostate cancer patients
6. Targeting cholesterol may help slow glioblastoma
7. Targeting cholesterol to fight deadly brain cancers
8. Targeting innate immunity in malaria
9. Targeting PTEN may prevent skin cancer
10. Targeting the Ewing sarcoma family of tumors
11. Latest data from Cedars-Sinai vaccine study supports immune targeting of brain tumors
Post Your Comments:
(Date:11/26/2015)... ... November 26, 2015 , ... ... to discuss bioavailability and the need to integrate dose form selection in early ... with OBN, the membership organization supporting and bringing together the UK’s emerging life ...
(Date:11/26/2015)... Aliso Viejo, CA (PRWEB) , ... November 26, ... ... X users a new set of retro-fused, self-animating trailer titles with ProTrailer: Vintage. ... custom style options. These classically-influenced trailer titles work with any font, giving users ...
(Date:11/25/2015)... ... November 25, 2015 , ... As part of a ... ™ attracts volunteers together who want to combine talents and resources to help ... in the process. The non-profit launched its first major fundraiser on November 6, ...
(Date:11/25/2015)... MN (PRWEB) , ... November 25, 2015 , ... ... launched offering factory direct sauna parts and accessories. , Sauna accessories help ... of the bather’s style and personality. From basic styles for the purist looking ...
(Date:11/25/2015)... ... November 25, 2015 , ... For the first time, Vitalalert is donating ... Beat ” campaign. The partnership between the two groups began in 2014 with Vitalalert ... cause. , MAP International was founded in 1954 and is an international Christian-based health ...
Breaking Medicine News(10 mins):
(Date:11/26/2015)... November 26, 2015 Un nuevo ... Bremachlorin para el cáncer avanzado.   --> ... terapia fotodinámica de Bremachlorin para el cáncer avanzado. ... la inmunoterapia con la terapia fotodinámica de Bremachlorin para ... Research . --> Clinical Cancer Research . ...
(Date:11/26/2015)... , November 26, 2015 --> ... to use SyMRI to find optimal contrast weighting of MRI ... metastases, and has signed a research agreement with SyntheticMR in ... hospital. Using SyMRI, it is possible to generate multiple contrast ... after the patient has left, thus making it possible to ...
(Date:11/26/2015)... November 26, 2015 ... the "2016 Future Horizons and Growth ... Testing Market: Supplier Shares, Country Segment Forecasts, ... their offering. --> ) ... "2016 Future Horizons and Growth Strategies in ...
Breaking Medicine Technology: