New developments reveal a molecule with a promising function in terms of cancer treatment.

October 30, 2012

Researchers from Inserm and CNRS from the Institute for genetics and molecular and cellular biology (IGBMC) and from the Research Institute at the Strasbourg school of biotechnology (Irebs) have focussed their efforts on PARG, currently thought to be a promising new therapeutic target in the treatment of cancer. Their work has revealed the role of this molecule in regulating gene expression. The results were published on 25 October 2012 in the on-line Molecular Cell review.

Cells are subjected to various stresses throughout their life. Some of this stress can damage DNA. Fortunately, cells have several mechanisms used to repair these lesions. Breaking two is one of the most serious afflictions a chromosome can suffer. The cell must repair this break if it is to continue dividing. Repair actions are either performed in an optimal manner, and the cell resumes its normal division cycle, or the lesion is not repaired correctly, causing the cell to die or the appearance of an anomaly that may trigger cancer.

One of the repair mechanisms used is poly(ADP-ribosyl)ation. In this mechanism, some molecules (PARPs) detect DNA breaks and cause poly(ADP-riboses) synthesis that binds with proteins, thus initialising the lesion repair system. As such, this system can act as a 'saviour' if the repairs are correctly completed, but, it can be equally damaging in the event of incorrect repair.

In the case of cancer, to ensure the cells are destroyed, PARP inhibitors are currently undergoing clinical tests as therapeutic adjuvant used to increase the receptivity of to specific chemotherapies.

In terms of fundamental research, researchers know that the poly(ADP-ribosyl)ation mechanism is reversible and is closely regulated by Poly(ADP-ribose) glycohydrolase (PARG). PARP and PARG thus seem to make up a tandem of molecules dedicated to maintaining genome integrity. PARG targeting has proved to potentiate the action of genotoxic agents, making this molecule a promising new in the treatment of some cancers, as is the case for PARP.

However, little research has been conducted into PARG, but in light of its close links with PARP, researchers are now taking a very close look at its functions.

In this new work, the researchers have demonstrated that in addition to its genome repair role, PARG was involved in modulating the cell's transcriptional activity.

Given the keen current interest on PARP and PARG inhibitors in the , it is essential to gain accurate knowledge of the functions and action modes of these promising therapeutic targets, as well as the consequences of their invalidation. This study is the first to highlight how PARG action mechanism regulates .

Explore further: Bacteria shed light on new drug targets for inherited cancers

Related Stories

Bacteria shed light on new drug targets for inherited cancers

September 6, 2011
Cancer Research UK scientists have succeeded in purifying a protein found in bacteria that could reveal new drug targets for inherited breast and ovarian cancers - and other cancers linked to DNA repair faults. The study ...

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

June 27, 2011
(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 may have clinical utility in HER2-positive breast cancers

September 17, 2012
Poly (ADP-Ribose) polymerase (PARP) inhibitors, shown to have clinical activity when used alone in women with familial breast and ovarian cancers linked to BRCA mutations, may be a novel treatment strategy in women with HER2-positive ...

'PARP' drug sabotages DNA repair in pre-leukemic cells

December 12, 2011
Looking for ways to halt the uncontrolled growth of cancer cells, scientists at Johns Hopkins have found that a new class of drugs, called PARP inhibitors, may block the ability of pre-leukemic cells to repair broken bits ...

Blocking molecular target could make more cancers treatable with PARP inhibitors

June 29, 2011
BOSTON--Researchers at Dana-Farber Cancer Institute have demonstrated a molecular strategy they say could make a much larger variety of tumors treatable with PARP inhibitors, a promising new class of cancer drugs.

Recommended for you

CAR-T immunotherapy may help blood cancer patients who don't respond to standard treatments

October 20, 2017
Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine in St. Louis is one of the first centers nationwide to offer a new immunotherapy that targets certain blood cancers. Newly approved ...

Researchers pinpoint causes for spike in breast cancer genetic testing

October 20, 2017
A sharp rise in the number of women seeking BRCA genetic testing to evaluate their risk of developing breast cancer was driven by multiple factors, including celebrity endorsement, according to researchers at the University ...

Study shows how nerves drive prostate cancer

October 19, 2017
In a study in today's issue of Science, researchers at Albert Einstein College of Medicine, part of Montefiore Medicine, report that certain nerves sustain prostate cancer growth by triggering a switch that causes tumor vessels ...

Gene circuit switches on inside cancer cells, triggers immune attack

October 19, 2017
Researchers at MIT have developed a synthetic gene circuit that triggers the body's immune system to attack cancers when it detects signs of the disease.

One to 10 mutations are needed to drive cancer, scientists find

October 19, 2017
For the first time, scientists have provided unbiased estimates of the number of mutations needed for cancers to develop, in a study of more than 7,500 tumours across 29 cancer types. Researchers from the Wellcome Trust Sanger ...

Researchers target undruggable cancers

October 19, 2017
A new approach to targeting key cancer-linked proteins, thought to be 'undruggable," has been discovered through an alliance between industry and academia.

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.