Genetic Research Studies the "On / Off" Switches for Cancer

Apr 16, 2015

An initiative toward more individualized and effective treatments for cancer is gaining traction at universities in Virginia.

WMRA’s David Doremus reports that researchers here are studying the way DNA actually works.  The initiative drew President Obama’s attention in this year’s State of the Union address.

PRESIDENT OBAMA:  So tonight, I’m launching a new Precision Medicine Initiative to bring us closer to curing diseases like cancer and diabetes, and give all of us access

to the personalized information we need to keep ourselves and our families healthier.

That’s President Obama … announcing the initiative in January. It represents an innovative approach to disease prevention and treatment that takes into account individual differences in people’s genes, environments, and lifestyles.

Of course, we all know that lifestyle choices can have a direct impact on our health. But a genetic predisposition to a certain disease is something we’ve tended to see as just bad luck. New findings in the field of epigenetics, however, suggest we may have more control over disease-causing processes at the level of our DNA than previously thought.

Epigenetics looks at changes in the way genes express themselves that are linked to things we eat and drink, environmental toxins, and the stress of life-events. Local scientists are among those studying whether our daily routines activate epigenetic "on-off" switches for cancer and other diseases. Ray Enke, assistant professor of biology at James Madison University, explains that you don’t need to change the DNA itself to change how genes are expressed.

RAY ENKE:      Epigenetic modifications to the genome are sort of small chemical modifications that can be added to and subtracted from. They don't change the sequence of the genome, but they can change the functionality. So these epigenetic modifications are affecting which genes are turned on, and which genes are turned off.

If the human genome is the how-to manual for building an individual person, the epigenome can be thought of as the cross-outs and highlighting that tell us how to interpret the book and act on its instructions.

One major type of epigenetic modification has to do with the way DNA is packaged inside cell nuclei. Each cell starts out with the same DNA, but the functions the DNA performs depend on how it is packaged up inside the nucleus, and where the resulting folds and loops occur. Folding determines function, says Anindya Dutta, chairman of biochemistry and molecular genetics at the University of Virginia ….

ANINDYA DUTTA:    The reason why my skin cell is different from my brain cell ... despite the DNA being exactly the same DNA I received from my parents ... is that the packaging of the DNA is completely different in the two cells.

With the publication in February of a 3-D map of the human genome, researchers have arrived at a better understanding of the three-dimensional shape of normally packaged DNA. Now that we know how the genome is supposed to be packaged, we can start to modify its shape. It’s possible the root cause of at least some cancers is an abnormal shape that turns a normal gene into a cancer-causing oncogene. UVa’s Dutta compares it to the gas pedal on a car.

DUTTA:    Without it, the car wouldn't move. Without oncogenes performing their normal functions, cells wouldn't be able to divide. But the gas pedal becomes an oncogene when it's stuck in the ‘on’ position.

While it may be scary to think that the epigenetic amplification or silencing of critical genes can turn normal cells into cancerous ones, it’s also good news. The traditional view has been that cancer is a disease that arises only from broken genes, which are harder to fix than the epigenetic tags that turn genes “on” and “off.” In fact, we already have a few drugs that have been shown effective when directed against epigenetic mechanisms of disease.

The vastness and complexity of these phenomena at the molecular has prompted researchers to enlist the help of bioinformatics, which uses digital tools such as machine learning, statistics, and algorithms to better understand the behavior of cells. JMU’s Ray Enke says the generation of life-scientists whose job it will be to deliver on the promise of precision medicine – providing the right treatments, at the right time, to the right person, every time – will need thorough exposure to this emerging field.

ENKE:      We're trying to equip our students with at least some baseline skills for how to look at large data sets, analyze large data sets, how to do an experiment not only at a lab bench, in sort of a ‘wet lab’ setting, but also a computer-based bioinformatics experiment.

Big Data is expected to play a key role in the precision medicine initiative. And even more powerful digital tools will be needed to manage and analyze the huge quantities of data generated by precision medicine research.