A gene implicated in the development of cancer cells can be switched on using drugs, report researchers from the University of Michigan Comprehensive Cancer Center. The finding could lead to a new class of targeted cancer therapies with potential to benefit many different cancer types.
Popular new drugs such as Herceptin and Gleevec more effectively treat cancer by targeting genetic mutations that express themselves in large amounts, causing cancer to develop. But cancers also arise because genes that control growth are turned off. While researchers can use these turned-off genes to identify or monitor cancer, currently no treatments actually target these genes.
U-M researchers found that a gene called Brahma, or BRM, is silent – but not missing – in some cancer cells. By exposing the BRM protein to an inhibitor drug, the researchers were able to turn the gene back on, allowing BRM to be expressed. The researchers found this gene is turned off in about 15 percent of tumors studied, including cells from lung, esophageal, ovarian, bladder, colon and breast cancers.
The researchers were able to use existing drugs, which showed some usefulness in turning on the BRM gene. But new drugs would need to be developed to be more effective in reactivating this gene in cancer cells. Still, researchers are excited about the potential this finding could have in leading to new targets for cancer treatment.
“This is a targetable target. We can detect it, but we need to find a better way to turn it back on. No drugs are designed to deal with a gene that’s turned off. But it’s a straightforward extension of current therapies that target genes that are turned on,” says lead study author David Reisman, M.D., Ph.D., assistant professor of internal medicine at the U-M Medical School.
Results of the study appear in the advanced online publication of the journal Oncogene.
The researchers sought to understand why BRM is not expressed in certain cancer cell lines. They found no mutations to the gene but rather that it was just silent – essentially like a switch that had been turned off. Knowing that a class of drugs called histone deacetylase inhibitors, or HDAC inhibitors, can affect gene expression, the researchers applied these drugs to the cells and found the BRM expression could be restored – like flipping the switch back on.
While the existing HDAC inhibitors did return BRM expression, the effect was short-lived. Once the drugs were taken away, BRM expression decreased.
“The HDAC inhibitors are not the perfect answer, but in principle this tells us we can turn our gene back on. If we can turn the gene back on, it may not be a cure for cancer, but it could slow it down or make it responsive to existing drugs,” Reisman says.
The researchers targeted lung cancer cell lines in particular, although they found similar results in a variety of other cancer cell lines tested. A potential target to treat lung cancer is particularly crucial as the death rate from lung cancer has not changed in 30 years. Newer treatments are much less toxic and extend lives by months, but the same people who died from lung cancer 30 years ago, would still succumb to this disease today.
Targeted therapies have dramatically improved cancer care in recent years, because they thwart the specific genes which drive the development and progress of cancers. They typically have few toxic side effects, unlike traditional chemotherapy, making them more tolerable as a long-term treatment or in combination with other drugs.
“Tumors are not the same from one person to the next, and even the cells within a single tumor are not the same. Giving a single drug or drug combination to 500 people is setting ourselves up for failure, much like a one-size-fits-all clothing store would never succeed,” Reisman says.
“Targeted therapies are now opening the door, because they are essentially given only to those patients who have a high likelihood of response. Their low toxicity means the patient can be treated for long periods of time, which is unlike older and more traditional chemotherapy agents. Even if these new targeted therapies don’t cure the cancer, we can at least have long-term survival,” he adds.
Nicole Fawcett | EurekAlert!
Molecular microscopy illuminates molecular motor motion
26.07.2017 | Penn State
New virus discovered in migratory bird in Rio Grande do Sul, Brazil
26.07.2017 | Fundação de Amparo à Pesquisa do Estado de São Paulo
Strong light-matter coupling in these semiconducting tubes may hold the key to electrically pumped lasers
Light-matter quasi-particles can be generated electrically in semiconducting carbon nanotubes. Material scientists and physicists from Heidelberg University...
Fraunhofer IPA has developed a proximity sensor made from silicone and carbon nanotubes (CNT) which detects objects and determines their position. The materials and printing process used mean that the sensor is extremely flexible, economical and can be used for large surfaces. Industry and research partners can use and further develop this innovation straight away.
At first glance, the proximity sensor appears to be nothing special: a thin, elastic layer of silicone onto which black square surfaces are printed, but these...
3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects
A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...
Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.
For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...
What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.
To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...
26.07.2017 | Event News
21.07.2017 | Event News
19.07.2017 | Event News
26.07.2017 | Physics and Astronomy
26.07.2017 | Life Sciences
26.07.2017 | Earth Sciences