Inhibiting a DNA-repairing protein in brain could be key to treating aggressive tumors

January 10, 2017

Targeting a specific DNA-repairing protein in the brain could be an effective way to treat the most aggressive type of brain tumour, a study suggests.

Researchers at the University of Leeds found that inhibiting this protein, called RAD51, helped increase the effectiveness of radiotherapy in killing off glioblastoma cells in the lab.

Glioblastoma is the most common type of primary in adults and also the most aggressive. Many patients will not survive their disease despite intensive treatment.

It's thought a subgroup of glioblastoma cells are able to reproduce to make identical copies of themselves and are more resistant to treatment.

In the new study, the researchers found that this subgroup of cells, called Glioblastoma Stem Cells (GSCs), have a large amount of the RAD51 inside them.

Professor Susan Short, Professor of Clinical Oncology and Neuro-Oncology at the University of Leeds and lead author of the study, said: "Radiotherapy damages the DNA in the glioblastoma cells - but the RAD51 helps them to repair this damaged DNA, meaning they can repopulate the tumour.

"By targeting RAD51 with an inhibitor we were able to make these GSCs more sensitive to the effects of radiotherapy, helping remove the tumour.

"The exact mechanism by which RAD51 becomes increased in cells that survive radiotherapy is not yet known but our study provides strong evidence that this is the right protein to target in the treatment of this aggressive cancer."

The researchers, whose study was published in the journal Stem Cell Reports, used brain tumour cells taken from patients.

They used immunofluorescence microscopy to show that the have higher amounts of RAD51 than other normal brain cells.

They then combined an inhibitor agent with radiation to target the cells.

"The next step will be to find an inhibitor agent that can be used on humans," said Professor Short.

"The inhibitors that we used are not yet suitable for clinical trials, but these results suggest that using equivalent agents or new drugs that target this same pathway will be important to investigate."

The study was funded by Cancer Research UK.

Dr Justine Alford, Cancer Research UK's senior science information officer, said: "Survival for glioblastoma is low and has seen little improvement over the years, so we urgently need better, kinder treatments for the disease.

"This promising study in and mice may have found a way to cut off the tumour's fuel supply, which could one day help treatments target the disease more precisely and effectively. But more research is needed to find out if this strategy could be safe and effective in people."

Glioblastoma primarily affects adults aged between 45 and 75 and is slightly more common in men than in women.

Unfortunately the prognosis for patients diagnosed with glioblastoma is poor.

The average survival time is 12 -18 months. Only 20% of patients survive more than one year, and only 3% of patients survive more than three years.

Explore further: Therapy response in brain tumor cells linked to disease prognosis

More information: Harry O. King et al, RAD51 Is a Selective DNA Repair Target to Radiosensitize Glioma Stem Cells, Stem Cell Reports (2017). DOI: 10.1016/j.stemcr.2016.12.005

Related Stories

Therapy response in brain tumor cells linked to disease prognosis

December 13, 2016
The brain tumour form glioblastoma is difficult to treat and has very poor prognosis. In a new study, published today in the journal Cell Reports, scientists from Uppsala University show that a type of stem cell in the tumour ...

New hope in fight against aggressive and often hard to treat brain tumour

September 23, 2016
Researchers from the University of Southampton have discovered a potential way of stopping one of the most aggressive types of brain tumour from spreading, which could lead the way to better patient survival.

Pathway linked to slower aging also fuels brain cancer

December 6, 2016
While a particular metabolic pathway shows potential to slow down the aging process, new research indicates a downside: That same pathway may drive brain cancer.

Researchers find new driver of an aggressive form of brain cancer

November 15, 2016
University of Hawai'i Cancer Center researchers have identified an essential driver of tumor cell invasion in glioblastoma, the most aggressive form of brain cancer that can occur at any age. The discovery can help researchers ...

Study reveals new information on how brain cancer spreads

November 17, 2016
Glioblastoma multiforme remains the most common and highly lethal brain cancer and is known for its ability to relapse. Researchers at The University of Texas MD Anderson Cancer Center have identified a pathway by which cancer ...

Study explains mechanisms behind glioblastoma influence on the immune system

September 12, 2016
Glioblastomas exert an influence on the microglia, immune cells of the brain, which causes them to stimulate cancer growth rather than attacking it. In a study published in the journal Nature Immunology, an international ...

Recommended for you

Stem cell therapy attacks cancer by targeting unique tissue stiffness

July 26, 2017
A stem cell-based method created by University of California, Irvine scientists can selectively target and kill cancerous tissue while preventing some of the toxic side effects of chemotherapy by treating the disease in a ...

Understanding cell segregation mechanisms that help prevent cancer spread

July 26, 2017
Scientists have uncovered how cells are kept in the right place as the body develops, which may shed light on what causes invasive cancer cells to migrate.

Study uncovers potential 'silver bullet' for preventing and treating colon cancer

July 26, 2017
In preclinical experiments, researchers at VCU Massey Cancer Center have uncovered a new way in which colon cancer develops, as well as a potential "silver bullet" for preventing and treating it. The findings may extend to ...

Compound shows promise in treating melanoma

July 26, 2017
While past attempts to treat melanoma failed to meet expectations, an international team of researchers are hopeful that a compound they tested on both mice and on human cells in a petri dish takes a positive step toward ...

Study may explain failure of retinoic acid trials against breast cancer

July 25, 2017
Estrogen-positive breast cancers are often treated with anti-estrogen therapies. But about half of these cancers contain a subpopulation of cells marked by the protein cytokeratin 5 (CK5), which resists treatment—and breast ...

Breaking the genetic resistance of lung cancer and melanoma

July 25, 2017
Researchers from Monash University and the Memorial Sloan Kettering Cancer Center (MSKCC, New York) have discovered why some cancers – particularly lung cancer and melanoma – are able to quickly develop deadly resistance ...

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.