Pharma Strategy Blog

Several links have begun to emerge relating both cancer and aging with the integrity of eukaryotic chromosome ends, called telomeres. Studies from several research laboratories have identified proteins involved in replicating and regulating telomere length and stability. The function of these telomere maintenance factors and their role in human disease are not yet fully established. One of the long term goals of scientists is to understand how telomeric complexes protect chromosome ends and mediate their replication and apply this information in pursuit of anticancer therapies.

In humans, telomerase adds repeated short sequences of DNA to the chromosomes ends/telomeres, protecting them froom damage and the loss of genetic information during cell division. This process sometimes gets faulty with age, explaining why the risk of many cancers increases with age. When telomerase is dormant, telomeres shorten each time a cell divides, leading to genetic instability and cell death. By preserving the chromosomes integrity, telomerase allows cells to continue living and dividing normally. The enzyme is active in cells that multiply frequently (eg embryonic stem cells) but switched off in normal adult cells to prevent cell proliferation. In many cancer cells, it is switched on, causing runaway cell growth.

Recently, researchers at the Wistar Institute have unravelled the structure of the active region of telomerase, an enzyme that plays a major role in development of many cancers. On August 31, an article appeared in Nature's Oncogene journal, describing the epigenetic factors that affect telomeres. This is an important piece of research because scientists have long been stumped how to find drugs that shut down telomerase because the enzymes structure and methylation function was unknown. It is active in many cancers but inactive in most normal cells, thereby making it a potential target.

Image Courtesy of UIC.edu

The Wistar Institute study identifies the active region of telomerase, provides the first view of the molecules critical protein component and how it replicates the ends of chromosomes, a process that is crucial to tumour development and the aging process.

The findings could mean that it may be possible to potentially convert immortal cancer cells back into normal mortal ones by blocking telomerase using drugs specifically developed to target the enzyme, thereby slowing or stopping the tumour growth.

Sources:

Wistar Institute, Philadelphia
BBC News
University of Illinois at Chicago