A progression mechanism found in 90 percent of cancers has been discovered, suggesting a new target for future therapies, a research team from Singapore suggests. The team believes that by preventing a reactivating enzyme that allows cancer cells to grow uncontrollably, targeted treatments could halt cancer progression with fewer side effects.
The research was published in Nucleic Acids Research.
As cells age, the protective "caps" on the end of our chromosomes begin to shorten. The caps, called telomeres, are incredibly important for the regular turnover of cells – once they become too short, the DNA is destroyed to make way for new, healthy cells. Through this, cells cannot build up enough mutations over their lifespan to become problematic.
Cancer, however, doesn’t want the body destroying cells that have mutated to grow uncontrollably, so cancerous tumors reactivate an enzyme called telomerase to maintain the length of the telomeres.
Current research knows all too well about telomerase, and also how cancer does it – through activating the Human Telomerase Reverse Transcriptase (hTERT) gene. If a therapy can stop the activation of telomerase, which is mostly inactive apart from cancer cells, it could stop tumor growth with relatively few problems.
But how do cancer cells activate hTERT so readily? This is the focus of a new piece of research, which has discovered a region of DNA crucial for activating hTERT in primary colorectal cancers that is only present in cancer cells. This region is involved in interacting with a promoter region of hTERT and, alongside other elevated proteins, ultimately activating the gene. It is the first study to dive into the details of hTERT activation through this mechanism.
“Activation of telomerase is the most common oncogenic event providing immortality to cancer cells. We now know how to inhibit telomerase activity to target cancer cells specifically. This study will be a guide for developing next-generation cancer inhibitors,” said Semih Akincilar, lead researcher of the study, in a statement.
Telomerase inhibition, through any number of pathways, is an attractive target for cancer prevention, but it is still in its infancy. Current therapies targeting telomerase often come with side effects, including some that increase the chance of cardiomyopathy, so the pursuit of a safe alternative is incredibly important.
The researchers hope that using the patient-derive colorectal cancer cells and their new understanding of hTERT activation, they can begin to create targeted telomerase inhibitors that may have more success than previous options.