Breakthrough could make 'smart drugs' effective for many cancer patients

June 27, 2011 in Cancer
Breakthrough could make 'smart drugs' effective for many cancer patients

(Medical Xpress) -- Newcastle and Harvard University reseachers have found that blocking a key component of the DNA repair process could extend the use of a new range of 'smart' cancer drugs called PARP inhibitors.

PARP inhibitors have been showing great promise in for patients with breast, ovarian and caused by in a gene called BRCA1. They work by blocking the action of PARP – a molecule involved in the repair of damaged DNA.

By themselves, PARP inhibitors are unable to kill but when used to target cancer cells that lack a protein normally produced by the BRCA1 gene, which is also involved in , the two factors act together to attack the cancer cell. They are no longer able to repair DNA damage, ultimately leading them to die.

But, BRCA deficient cancers only account for a small proportion of all cancers. To improve the effectiveness and range of PARP inhibitors the researchers looked at whether artificially recreating the effect of losing BRCA1 by blocking a key controller of the cell cycle, Cdk1, would have the same effect.

Cdk1 plays an important role in repairing DNA by switching on BRCA1 in response to DNA damage. So when the researchers blocked the action of Cdk1 and treated the cells with PARP inhibitors the same two-pronged effect was seen in cells not previously affected by PARP inhibitors. The research is published in Nature Medicine.

Professor Nicola Curtin from Newcastle University, whose early work, funded by Cancer Research UK, linked PARP inhibitors and BRCA mutations, said: “Our research shows how blocking Cdk1 compromises DNA repair in cancer cells, making them sensitive to PARP inhibitors. We were also able to show that this approach only targeted cancer cells, so if we are able to develop an effective Cdk1 drug we could have a more targeted treatment with fewer side effects.

“Now we need to take this research in the lab and develop an effective drug that can block Cdk1, so more patients can benefit from treatment with PARP inhibitors.” 

Dr Lesley Walker, director of cancer information at Cancer Research UK, said: “Cancer Research UK scientists have played a central role over the past two decades in developing PARP . While they were originally designed to enhance the DNA damaging effects of chemotherapy and radiotherapy on cancer cells, where part of the DNA repair mechanism was already damaged, we are seeing they could be used to treat a wider range of cancers than previously thought. If the researchers are able to develop an effective drug to block Cdk1 we could have a powerful new tool to treat cancer patients.”

More information: Johnson, N et al, Compromised CDK1 activity sensitizes BRCA-proficient cancers to PARP inhibition, Nature Medicine (2011)

Provided by Newcastle University

5 /5 (1 vote)  

Rank 5 /5 (1 vote)
Related Stories
Relevant PhysicsForums posts
  • A question about drug tolerance
    created21 hours ago
  • Poor nutrition leading to overeating?
    createdMay 23, 2012
  • Math and dyslexia?
    createdMay 21, 2012
  • portable metabolism meter?
    createdMay 21, 2012
  • Rare medical conditions on 20/20 tonight
    createdMay 18, 2012
  • "Good" Cholesterol in Doubt
    createdMay 17, 2012
  • More from Physics Forums - Medical Sciences

More news stories

Childhood cancer scars survivors later in life

Scars left behind by childhood cancer treatments are more than skin-deep. The increased risk of disfigurement and persistent hair loss caused by childhood cancer and treatment are associated with emotional distress and reduced ...

Cancer created 34 minutes ago | popularity not rated yet | comments 0

Amino acid consumption associated with how fast cancer cells divide

For almost a century, researchers have known that cancer cells have peculiar appetites, devouring glucose in ways that normal cells do not. But glucose uptake may tell only part of cancer's metabolic story. Researchers from ...

Cancer created 43 minutes ago | popularity not rated yet | comments 0 | with audio podcast

Marked for destruction: Newly developed compound triggers cancer cell death

The BCL-2 protein family plays a large role in determining whether cancer cells survive in response to therapy or undergo a form of cell death known as apoptosis. Cells are pressured toward apoptosis by expression of pro-apoptotic ...

Cancer created 4 hours ago | popularity 5 / 5 (1) | comments 0

Thioridazine kills cancer stem cells in human while avoiding toxic side-effects of conventional cancer treatments

A team of scientists at McMaster University has discovered a drug, thioridazine, successfully kills cancer stem cells in the human while avoiding the toxic side-effects of conventional cancer treatments.

Cancer created 4 hours ago | popularity 4.8 / 5 (8) | comments 1 | with audio podcast

Study links mental health problems to poor prognosis in male cancer patients

Men suffering from psychiatric problems when diagnosed with cancer are more likely to die from the disease, according to a new study part-funded by the Wellcome Trust. The findings also reveal that those with ...

Cancer created 7 hours ago | popularity not rated yet | comments 0


Cyber exercise partners help you go the distance: Motivation gains can double

A new study testing the benefits of a virtual exercise partner shows the presence of a moderately more capable cycling partner can significantly boost the motivation – by as much as 100 percent – ...

Low vitamin D in diet increases stroke risk in Japanese-Americans

Japanese-American men who did not eat foods rich in vitamin D had a higher risk of stroke later in life, according to results of a 34-year study reported in Stroke, an American Heart Association journal.

Doctors group warns EU health care access shrinking

Access to health care is declining in Europe, and Greece in particular faces a humanitarian crisis as it cuts health and social spending, aid group Doctors of the World warned Thursday.

Scotland sets minimum price for booze

Scotland on Thursday became the first part of Britain to introduce a minimum price for alcohol in an attempt to change its unhealthy relationship with booze.

Researchers identify protein necessary for behavioral flexibility

Researchers have identified a protein necessary to maintain behavioral flexibility, which allows us to modify our behaviors to adjust to circumstances that are similar, but not identical, to previous experiences. Their findings, ...

Boundary stops molecule right where it needs to be

A molecule responsible for the proper formation of a key portion of the nervous system finds its way to the proper place not because it is actively recruited, but instead because it can't go anywhere else.