Navigation Links
Scientists find promising new approach to preventing progression of breast cancer

LA JOLLA, CA February 15, 2013 Doctors currently struggle to determine whether a breast tumor is likely to shift into an aggressive, life-threatening modean issue with profound implications for treatment. Now a group from The Scripps Research Institute (TSRI) has identified a mechanism through which mitochondria, the powerhouses of a cell, control tumor aggressiveness. Based on their findings, the team developed a simple treatment that inhibits cancer progression and prolongs life when tested in mice.

The research team, which describes its results February 15, 2013, in an article published online ahead of print by The Journal of Clinical Investigation, hopes to proceed quickly to human clinical trials to test this new approach using drugs already in use for other conditions.

Looking at Clues

The TSRI laboratory of Associate Professor Brunhilde H. Felding studies cancer, especially the mechanisms that control metastasis, the spread of cancer from its primary site to distant organs in the body.

Past research suggested that mutations affecting mitochondria, which are key to energy production in cells, strongly influence whether a tumor becomes aggressive. But the mechanism was not clear.

"We decided to investigate a specific protein complex, called mitochondrial complex I, that critically determines the energy output of cellular respiration," said the study's first author, Antonio F. Santidrian, a research associate in Felding's laboratory. To do this, the group teamed up with Akemi and Takao Yagi at TSRI, who are leading experts in complex I research. Using unique reagents from the Yagi group, the Felding team discovered that the balance of key metabolic cofactors processed by complex Ispecifically, nicotinamide adenine dinucleotide (NAD+) and NADH, the form it takes after accepting a key electron in the energy production cyclewas disturbed in aggressive breast cancer cells.

Exciting Results

To find out if the balance of NAD+ and NADH was critical for tumor cell behavior, the team proceeded to insert a yeast gene into cancer cells that caused a shift toward more NAD+. To the scientists' amazement, this shift caused the tumor cells to become less aggressive.

"It was a really happy moment for me," said Santidrian. But the more exciting moments, he said, were yet to come.

To confirm and extend the initial findings, the team altered genes tied to NAD+ production. The resulting shift again showed that higher NADH levels meant more aggressive tumors, while increased NAD+ had the opposite effect.

The next logical step was to find a simple way to enhance the critical NAD+ level therapeutically. So the team explored what would happen if mice with breast cancer were fed water spiked with nicotinamide, a precursor for NAD+ production. The scientists found cancer development was dramatically slowed down, and the mice lived longer

"In animal models at various stages, we see that we can actually prevent progression of the disease," said Felding.

Next Steps

Now the group is working toward human trials to learn whether nicotinamide or other NAD+ precursors will have similarly impressive results in humans. Since NAD+ precursors are already used for other purposes, such as controlling cholesterol levels, achieving approval for human clinical trials should be simpler than is normally the case.

"It is not a totally new treatment that would need to be tested for toxicity and side effects like a new drug," said Felding. "And we already know the precursors can be easily ingested."

If manipulating the NAD+/NADH ratio in humans has the same effect as in mice, the results could be profound. Such treatment could benefit people at risk of developing aggressive breast cancer, offer complimentary treatment to chemo and radiation therapy to avoid disease recurrence, and maybe even provide a preventive treatment for women with a family history of breast cancer.


Contact: Mika Ono
Scripps Research Institute

Related medicine news :

1. Hopkins scientists create method to personalize chemotherapy drug selection
2. Spanish scientists develop a pioneering technique to effectively treat mucositis
3. Scientists find calcium is the initial trigger in our immune response to healing
4. Scientists should advance management of behavioral norms
5. Scientists advance the art of magic with a study of Penn and Tellers cups and balls illusion
6. CSHL scientists identify a new strategy for interfering with a potent cancer-causing gene
7. Scientists Find 24 New Genes Linked to Nearsightedness
8. NIH scientists discover promising target to block Staphylococcus infection
9. Scientists find key to growth of bad bacteria in inflammatory bowel disease
10. Scientists Explore How Zinc Fights Off Infection
11. Compound developed by scientists protects heart cells during and after attack
Post Your Comments:
Related Image:
Scientists find promising new approach to preventing progression of breast cancer
(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 , ... According to an ... is being more and more widely heralded as a breakthrough for performing hernia repairs. ... has over traditional laparoscopic surgery is that it can greatly reduce the pain that ...
(Date:11/25/2015)... ... November 25, 2015 , ... The McHenry County law ... successful appellate decision obtained by Attorneys Francisco J. Botto and Alex C. Wimmer. Attorneys ... Workers’ Compensation Comm’n, 2015 IL App (2d) 130884WC. , According to court documents, Adcock ...
(Date:11/25/2015)... ... November 25, 2015 , ... Brillianteen, McGaw YMCA’s student-produced musical ... its 65th Anniversary Brillianteen Revue, scheduled for March 4-6, 2016. Auditions for this ... Brillianteen has been a treasured tradition for numerous families in the Evanston community. ...
(Date:11/25/2015)... Spring, Md (PRWEB) , ... November 25, 2015 ... ... Pulmonary Hypertension Association (PHA) announces the nation’s Periwinkle Pioneers, individuals and groups responsible ... history of this disease. The Periwinkle Pioneers, nominated by the public, will receive ...
Breaking Medicine News(10 mins):
(Date:11/24/2015)...  Array BioPharma Inc. (Nasdaq: ARRY ) ... Ron Squarer , will present at the Piper ... public is welcome to participate in the conference ... Jaffray Annual Healthcare ConferencePresenter:  , Ron Squarer, Chief ... Eastern Time Webcast: , ...
(Date:11/24/2015)... , 24. November 2015 ... Breathing Pacemaker Systems, ist erfreut, die Berufung ... Consultant bekannt geben zu können. ...   --> Foto - ... (Schweden). Von 1984-1986 war er Fellow ...
(Date:11/24/2015)... COMMACK, N.Y. , Nov. 24, 2015 ... Pacemaker System, is pleased to announce the appointment of ... ... and pediatric cardiology at Children,s Hospital, Uppsala University, Uppsala ... . From 1984-1986, he was a fellow at the ...
Breaking Medicine Technology: