Cancer cells learn to cope with large scale DNA changes.
Scientists have uncovered 2 ways in which cancer cells survive and grow, despite gene abnormalities.
When unfixable mistakes occur in the genes of healthy cells, they are programmed to self-destruct. However, cancer cells can continue to grow despite these damages. Over time, genetic changes allow cancer cells to keep growing, spreading, and to become resistant to treatment.
Two studies, published in Cancer Cell and Cancer Discovery, revealed 2 ways cancer cells are able to survive and grow during the genetic chaos.
The results of 1 study showed that bowel cancer cells with an abnormal number of chromosomes had a higher number of faults in the BCL9L gene. In normal cells, BCL9L activates the caspase-2 protein in response to the abnormal number of chromosomes, causing them to self-destruct.
However, the investigators found that by inactivating the BCL9L gene, the cells with an uneven number of chromosomes did not activate caspase-2 and continued to grow.
The findings suggest that errors in the BCL9L allows bowel cancer cells to adjust to the abnormal number to chromosomes, and continue to evolve and thrive, according to the authors.
Although cancer cells often make errors when dividing that allows them to continue to survive, too many errors can cause them to die.
In the second study, investigators found that faults in the APC/C helps cancer cells to slow down the division process to avoid making too many mistakes when distributing chromosomes to daughter cells. This process helps the cancer cells create a genetic diversity between the cells within the tumor.
“The development and progression of cancer is fueled by an unstable genome,” said lead investigator Charles Swanton. “It can cause a high degree of diversity between cells, influencing how well treatments work and drug resistance. If a cancer cell can cope with large scale changes to its DNA, then it might gain an advantage that helps it to grow, spread, and survive treatment. Until now, we knew very little about how these cancer cells kept growing and evolving. We hope that understanding these mechanisms will allow us to limit drug resistance and improve the efficacy of cancer therapies.”
The study’s findings open the door for developing new treatments that exploit the genetic chaos within cancer cells, the authors concluded.