Study finds missing piece of pediatric cancer puzzle

July 19, 2013, Nationwide Children's Hospital

Most of the time, it takes decades of accumulating genetic errors for a tumor to develop. While this explains the general occurrence of cancer in adults, it leaves a gap in understanding of the cause of pediatric tumors.

In a study published in the July issue of the Proceedings of the National Academy of Sciences, researchers found a missing piece of the pediatric cancer puzzle. Changxian Shen, PhD, senior research associate at the Center for Childhood Cancer and Blood Diseases at The Research Institute at Nationwide Children's Hospital, and Peter Houghton, PhD, director of the center, may have identified one mechanism behind the early development of some pediatric solid tumors – as well as a target for future therapies.

In healthy cells, a checkpoint prompts the cell to repair damaged DNA before it replicates. Many researchers believe that flourish when these checkpoints are skipped or inhibited, as the mutated cells can survive and rapidly reproduce. A growing collection of damaged cells can lead to the solid tumors of many childhood cancers, such as those of rhabdomyosarcoma, neuroblastoma and .

In their study, Drs. Shen and Houghton found that dampening a particular feedback loop between a repair checkpoint and its controlling pathways may promote the growth of tumors.

"Our prior studies had shown that the DNA damage checkpoint protein, ATM, was very low in most pediatric solid tumors," Dr. Houghton, also a faculty member at The Ohio State University College of Medicine, said. "The question was why?"

The study revealed that a number of problems may be at play in the development of pediatric solid tumors. First, a pathway called mTOR regulates the production of a cancer-causing gene that tells the cell to produce too much of two kinds of microRNAs. These microRNAs, in turn, suppress the synthesis of ATM, which makes it hard for cells to initiate the damage checkpoint. Low levels of ATM allow the mTOR pathway to keep producing the microRNAs that further reduce the ATM-mediated checkpoint activity. When the microRNAs weaken the cell's damage checkpoint, the checkpoint cannot effectively prevent mutated cells from proliferating.

By making this connection, Drs. Shen and Houghton have identified a potential explanation for the early development of pediatric tumors as well as a potential target for new cancer therapies. Early tumor growth seems to be caused by cells' rapid bypass of the damage checkpoints instead of the gradual accumulation of damage at play in adult tumor growth. Future treatments that can help cells increase ATM checkpoint activity or fight the overproduction of microRNAs may slow or stop the growth of cancerous pediatric tumors.

"These results help us to not only understand the early genesis of some tumors in children, but also why many solid tumors are highly sensitive to drugs and ionizing radiation that damage DNA," Dr. Houghton said. "They also help explain why, in children not cured by these treatments, resistance to therapy arises – the rapid rate of mutation due to suppression of ATM. Potentially, the rate of mutations that lead to drug or radiation resistance could be slowed by targeting mTOR."

Explore further: Researchers exploit cancer's faulty defence mechanism

Related Stories

Researchers exploit cancer's faulty defence mechanism

June 13, 2013
Researchers in Germany have found a new way to exploit the differences between cancer cells and normal cells that could lead to new treatments.

Nano drug crosses blood-brain tumor barrier, targets brain tumor cells and blood vessels

July 17, 2013
(Phys.org) —An experimental drug in early development for aggressive brain tumors can cross the blood-brain tumor barrier and kill tumor cells and block the growth of tumor blood vessels, according to a recent study led ...

New drug enhances radiation treatment for brain cancer in preclinical studies

May 14, 2013
A novel drug may help increase the effectiveness of radiation therapy for the most deadly form of brain cancer, report scientists at Virginia Commonwealth University Massey Cancer Center. In mouse models of human glioblastoma ...

New understanding of why anti-cancer therapy stops working at a specific stage

June 24, 2013
Researchers at the Hebrew University of Jerusalem and in California have achieved a breakthrough in understanding how and why a promising anti-cancer therapy has failed to achieve hoped-for success in killing tumor cells. ...

New findings regarding DNA damage checkpoint mechanism in oxidative stress

June 14, 2013
In current health lore, antioxidants are all the rage, as "everybody knows" that reducing the amount of "reactive oxygen species"—cell-damaging molecules that are byproducts of cellular metabolism—is critical to staying ...

Absence of specific enzyme in cartilage can lead to benign tumors in mice

July 18, 2013
Rhode Island Hospital researchers have found that the absence of the Shp-2 enzyme near specialized cartilage cells can lead to the development of multiple benign cartilage tumors in mice, a model that recapitulates the rare ...

Recommended for you

How cancer metastasis happens: Researchers reveal a key mechanism

January 18, 2018
Cancer metastasis, the migration of cells from a primary tumor to form distant tumors in the body, can be triggered by a chronic leakage of DNA within tumor cells, according to a team led by Weill Cornell Medicine and Memorial ...

Modular gene enhancer promotes leukemia and regulates effectiveness of chemotherapy

January 18, 2018
Every day, billions of new blood cells are generated in the bone marrow. The gene Myc is known to play an important role in this process, and is also known to play a role in cancer. Scientists from the German Cancer Research ...

These foods may up your odds for colon cancer

January 18, 2018
(HealthDay)—Chowing down on red meat, white bread and sugar-laden drinks might increase your long-term risk of colon cancer, a new study suggests.

The pill lowers ovarian cancer risk, even for smokers

January 18, 2018
(HealthDay)—It's known that use of the birth control pill is tied to lower odds for ovarian cancer, but new research shows the benefit extends to smokers or women who are obese.

Researchers develop swallowable test to detect pre-cancerous Barrett's esophagus

January 17, 2018
Investigators at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center have developed a simple, swallowable test for early detection of Barrett's esophagus that offers promise ...

Scientists zoom in to watch DNA code being read

January 17, 2018
Scientists have unveiled incredible images of how the DNA code is read and interpreted—revealing new detail about one of the fundamental processes of life.

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.