In a study headed by the Institute for Research in Biomedicine (IRB Barcelona), researchers found that drugs used to inhibit epigenetic factors may alter the number and pattern of mutations that tumors accumulate, which may be detrimental to patients. Although their anti-tumor effect may be beneficial initially, they can trigger the development of more aggressive tumors later on.
"We are not saying that this is going to happen in every case, but it is something that needs to be studied in greater depth before deciding whether drugs targeting epigenetic factors should be used in clinical practice or not," says Salvador Aznar Benitah, head of the Stem Cell and Cancer Laboratory at IRB Barcelona.
Cancer develops as a result of the accumulation of mutations in our cells. These mutations are not distributed evenly in our chromosomes, so some regions collect more than others. The research, published in Nature Cell Biology, examined whether the opening of chromatin is the factor that determines the difference in the accumulation of mutations across different regions.
This research indicates that the opening of chromatin leads to large genetic alterations, such as duplications and the loss of different regions of DNA. Because of this, at first, cancer cells were weakened and the tumors stopped growing when epigenetic factors were inhibited.
"This finding would make you think that epigenetic factors are good therapeutic targets,” says first author Alexandra Avgustinova, a postdoctoral fellow at IRB Barcelona. “But the genomic instability that occurred also brought about the appearance of mutated tumor cells, which eventually developed highly aggressive tumors."
Image: A invasive front of highly aggressive tumor cells (in green). Image courtesy of Alexandra Avgustinova, IRB Barcelona.