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

Study prompts new ideas on cancers' origins

December 16, 2017
Rapidly dividing, yet aberrant stem cells are a major source of cancer. But a new study suggests that mature cells also play a key role in initiating cancer—a finding that could upend the way scientists think about the ...

What does hair loss have to teach us about cancer metastasis?

December 15, 2017
Understanding how cancer cells are able to metastasize—migrate from the primary tumor to distant sites in the body—and developing therapies to inhibit this process are the focus of many laboratories around the country. ...

Cancer immunotherapy may work better in patients with specific genes

December 15, 2017
Cancer cells arise when DNA is mutated, and these cells should be recognized as "foreign" by the immune system. However, cancer cells have found ways to evade detection by the immune system.

Scientists pinpoint gene to blame for poorer survival rate in early-onset breast cancer patients

December 15, 2017
A new study led by scientists at the University of Southampton has found that inherited variation in a particular gene may be to blame for the lower survival rate of patients diagnosed with early-onset breast cancer.

Scientists unlock structure of mTOR, a key cancer cell signaling protein

December 14, 2017
Researchers in the Sloan Kettering Institute have solved the structure of an important signaling molecule in cancer cells. They used a new technology called cryo-EM to visualize the structure in three dimensions. The detailed ...

'Bet hedging' explains the efficacy of many combination cancer therapies

December 14, 2017
The efficacy of many FDA-approved cancer drug combinations is not due to synergistic interactions between drugs, but rather to a form of "bet hedging," according to a new study published by Harvard Medical School researchers ...

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.