Scientists discover metabolic pathway that drives tumor growth in aggressive cancers

March 2, 2017

Mount Sinai researchers have discovered that a rheumatoid arthritis drug can block a metabolic pathway that occurs in tumors with a common cancer-causing gene mutation, offering a new possible therapy for aggressive cancers with few therapeutic options, according to a study to be published in Cancer Discovery.

Ramon Parsons, MD, PhD, Ward-Coleman Chair in Cancer Research and Chair of the Department of Oncological Sciences at the Icahn School of Medicine at Mount Sinai, led a team that studied how a mutation of the PTEN gene rewires a in tumors, channeling increased amounts of the amino acid glutamine into the pathway, speeding up DNA production, and causing uncontrolled growth of the tumor. The team discovered that leflunomide, an oral rheumatoid arthritis drug approved by the U.S. Food and Drug Administration, blocks an enzyme in this pathway and damages the DNA created through the pathway, killing PTEN mutant cancer cells while leaving healthy cells untouched.

Parsons and his team transplanted human cells into mice to test leflunomide's efficacy. Leflunomide drastically reduced the breast cancer tumors in the mice.

"Finding successful targeted therapies for cancer is a challenging but important goal in the face of insufficient treatment options," said Dr. Parsons, who discovered the PTEN gene. "Targeted therapies that are tumor-specific are much needed, and identifying changes based on specific tumor suppressor or oncogene alterations will facilitate this effort. Due to the high mutation rate of PTEN in cancer, the effects of PTEN could be at the heart of targeted therapy."

This discovery has implications in aggressive cancers with the PTEN mutation and few treatment options such as triple negative breast cancer, prostate cancer, endometrial cancer, and glioblastoma, a brain cancer. Dr. Parsons hopes to create a clinical trial to further test leflunomide in patients with breast and colon .

Explore further: Gene variant may provide novel therapy for several cancer types

Related Stories

Gene variant may provide novel therapy for several cancer types

June 7, 2013
(Medical Xpress)—A novel gene variant found in human and animal tissue may be a promising treatment for cancer, including breast and brain cancer, according to scientists from the Icahn School of Medicine at Mount Sinai. ...

Researchers identify 'synthetic essentiality' as novel approach for locating cancer therapy targets

February 6, 2017
A new method has been found for identifying therapeutic targets in cancers lacking specific key tumor suppressor genes. The process, which located a genetic site for the most common form of prostate cancer, has potential ...

Newly discovered vulnerability in an aggressive breast cancer provides therapeutic target

March 2, 2017
Physicians currently have no targeted treatment options available for women diagnosed with an aggressive form of breast cancer known as triple-negative breast cancer (TNBC), leaving standard-of-care chemotherapies as a first ...

Researchers discover new combination therapy strategy for brain, blood cancers

February 28, 2017
Researchers at the University of Cincinnati (UC) College of Medicine have discovered a new potential strategy to personalize therapy for brain and blood cancers.

Researchers identify 'Achilles' heel' of PTEN that helps drive prostate cancer progression

February 13, 2017
Researchers at Cold Spring Harbor Laboratory (CSHL) have discovered that a protein called Importin-11 protects the anti-cancer protein PTEN from destruction by transporting it into the cell nucleus. A study they publish today ...

Accelerated discovery a triple threat to triple negative breast cancer

January 6, 2017
Houston Methodist Hospital researchers have advanced a potential treatment for metaplastic breast cancer—the most aggressive subtype of triple negative breast cancer, into patients in just under four years.

Recommended for you

Outdoor light at night linked with increased breast cancer risk in women

August 17, 2017
Women who live in areas with higher levels of outdoor light at night may be at higher risk for breast cancer than those living in areas with lower levels, according to a large long-term study from Harvard T.H. Chan School ...

Scientists develop novel immunotherapy technology for prostate cancer

August 17, 2017
A study led by scientists at The Wistar Institute describes a novel immunotherapeutic strategy for the treatment of cancer based on the use of synthetic DNA to directly encode protective antibodies against a cancer specific ...

Toxic formaldehyde is produced inside our own cells, scientists discover

August 16, 2017
New research has revealed that some of the toxin formaldehyde in our bodies does not come from our environment - it is a by-product of an essential reaction inside our own cells. This could provide new targets for developing ...

Cell cycle-blocking drugs can shrink tumors by enlisting immune system in attack on cancer

August 16, 2017
In the brief time that drugs known as CDK4/6 inhibitors have been approved for the treatment of metastatic breast cancer, doctors have made a startling observation: in certain patients, the drugs—designed to halt cancer ...

Researchers find 'switch' that turns on immune cells' tumor-killing ability

August 16, 2017
Molecular biologists led by Leonid Pobezinsky and his wife and research collaborator Elena Pobezinskaya at the University of Massachusetts Amherst have published results that for the first time show how a microRNA molecule ...

Popular immunotherapy target turns out to have a surprising buddy

August 16, 2017
The majority of current cancer immunotherapies focus on PD-L1. This well studied protein turns out to be controlled by a partner, CMTM6, a previously unexplored molecule that is now suddenly also a potential therapeutic target. ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.