Researchers from the University of Michigan Comprehensive Cancer Center suggest that drugs may be helpful in switching on a gene implicated in the development of cancer cells, raising hope for the development of a new class of targeted therapies with potential to benefit many different cancer types.
During the study, the researchers found that a gene called Brahma (BRM) was silent, but not missing, in some cancer cells. They found that the gene was turned off in about 15 percent of tumours studied, including cells from lung, oesophageal, ovarian, bladder, colon and breast cancers.
When the BRM gene was exposed to some of the existing inhibitor drugs, it was turned on. The finding attains significance because many times cancers occur when genes that control growth are turned off.
The researcher though concede that new drugs need to be developed to be more effective in reactivating this gene in cancer cells, they insist that their finding may lead 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 Dr. David Reisman, Assistant Professor of Internal Medicine at the U-M Medical School.
The study, published in the journal Oncogene, involved the use of a class of drugs called histone deacetylase inhibitors, or HDAC inhibitors.
While the existing HDAC inhibitors were found to switch on the BRM gene, the effect was short-lived and reduced as the drugs were taken away. "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. "Tumours are not the same from one person to the next, and even the cells within a single tumour 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.