Cells can adapt to overcome cancer drugs designed to interfere with their genetic controls, according to a study by Cancer Research UK scientists
. The findings were published in Epigenetics and Chromatin and reported in Drug Discovery & Development
The study showed that molecular “tags” are normally attached to DNA. These tags send signals to the cell, telling it how to package its DNA and switch genes on or off. Drugs that are known as HDAC inhibitors cause a build-up of certain types of tags, in turn causing potentially damaging changes in gene activity that can kill cancer cells. While these HDAC inhibitors can successfully treat certain types of cancer, such as lymphoma, other types have the ability to survive this disruption.
According to scientists from the University of Birmingham, cells accomplish this by activating an in-built “survival” response to HDAC inhibitors. The response rebalances the tags, maintaining normal gene activity and keeping the cells alive.
Researchers believe that these findings could help to identify which patients are suitable for treatment with these drugs. Additionally, the research could help develop future therapies that override the survival mechanism in tumor types that fail to respond.
According to lead author Dr. John Halsall, Cancer Research UK scientist from the University of Birmingham, “Our work has shown that some cancer cells can survive the gene damage caused by HDAC inhibitor drugs, so we’ve unveiled a new layer of the cancer cell’s defense that we need to target to destroy tumors. If we work out exactly which types of cancer are vulnerable to these drugs, we can use them in a smarter way to treat patients more effectively.”
Dr. Kat Arney, Cancer Research UK’s science information manager, added, “Working out how genes are switched on and off in cancer is vital if we’re to truly understand and beat the disease. This study could help us tailor how we use HDAC inhibitors so that more patients could benefit from them, and we’ll continue to work towards finding more effective ways to target cancer’s control mechanisms in the future.”