In this blog post, we’ll explore the scientific mechanisms behind how telomeres enable the unlimited division of cancer cells while also influencing human aging, along with the latest trends in therapeutic research.
A clue that could unlock the long-unresolved mystery of aging has recently been discovered: telomeres. Although telomeres are believed to be a cause of aging, the prospect of harnessing them to conquer aging offers hope. Meanwhile, telomeres are also present in cancer, one of the most deadly diseases threatening human health. However, telomeres—which cause human aging—exhibit a completely different response in cancer cells. In cancer cells, telomeres do not promote cellular aging. In this article, we will explore what telomeres are, what the unusual behavior observed in cancer cells entails and its underlying causes, and examine efforts to utilize this knowledge to combat cancer.
Telomeres refer to specific nucleotide sequences that are repetitively present at the ends of DNA strands to compensate for base loss during DNA replication. Our bodies constantly grow, heal wounds, and maintain the functions of internal organs through cell division. During this process, DNA is always replicated to ensure that both daughter cells receive identical DNA. However, due to functional issues with enzymes during DNA replication, an imbalance occurs where one strand of DNA becomes shorter. This means that as cell division repeats, the DNA strands gradually shorten, posing a risk of damage to genetic information. To defend against this, a structure called a telomere exists at the ends of DNA. These telomeres consist of repetitive sequences of seemingly meaningless nucleotides that can be discarded, and they prevent damage to important genetic information. However, as cell division continues, these telomeres eventually wear away completely. Consequently, many scientists believe that the secret to aging lies in these telomeres and are conducting research accordingly.
In contrast, a different phenomenon occurs in cancer cells. Cancer is a disease in which the regulatory mechanisms that normally limit cell growth do not function properly. Cells typically exchange signals with surrounding cells to regulate the rate of cell division. For example, cells in our bodies usually divide at a constant rate, but when an injury occurs in a specific area, more cell division takes place to repair the damaged tissue. However, in cancer cells, these regulatory mechanisms are impaired, causing them to divide continuously.
The key point is that cancer cells can divide almost indefinitely. In fact, cancer cells from Henrietta Lacks, who died of cervical cancer in the United States in 1951, were cultured in vitro and continue to divide to this day, serving as a model for numerous research studies. So why are cancer cells unaffected by the problem of DNA ends gradually shortening? The answer lies in an enzyme called telomerase. This enzyme is naturally active during the formation of germ cells. Germ cells are cells produced through meiosis; when male and female germ cells meet and fertilization occurs, a zygote is formed, and this zygote grows into a baby. Since genetic information does not change during meiosis, germ cells retain the exact genetic information of the somatic cell from which meiosis first occurred. However, somatic cells may already have shortened telomeres. Telomerase is what resolves this issue.
Telomerase acts as a type of reverse transcriptase that lengthens shortened telomeres. Reverse transcription is the process of creating DNA from RNA; telomerase uses an RNA strand complementary to the telomere strand to extend the shortened ends of chromosomes.
Normally, this enzyme is not active in somatic cells, but it becomes active during the formation of germ cells. However, most cancer cells use this telomerase to indefinitely extend their lifespan. Research has shown that telomerase is abnormally activated in most cancers. Thanks to this enzyme, cancer cells can maintain a structure that allows them to divide indefinitely without their telomeres shortening.
In theory, it seems that cancer could be conquered by developing drugs that reduce or eliminate the activity of telomerase within cancer cells. However, the reality is not that simple. First, telomeres can be regenerated by other means even without telomerase. For example, methods such as homologous recombination and DNA repair exist. These methods can extend the length of DNA or lengthen telomeres. Another problem is that even if telomere synthesis is blocked, it takes time for the telomeres to be completely depleted. During this time, cancer cells can continue to divide, making it difficult to take appropriate measures in the interim.
Since conquering cancer is not a simple problem to solve, researchers are continuing their research on telomere-related cancer treatments. Given that abnormal telomerase activity is found in about 90% of cancers, this could provide a crucial clue for cancer control. One such approach involves eliminating telomerase and then using the immune system to completely eradicate cancer cells. This method involves applying proteolytic enzymes to cancer cells to break down telomerase, causing the resulting fragments to attach to the surface of the cancer cells and act as antigens. This induces immune cells to recognize these antigens and attack the cancer cells.
Although this treatment was developed through extensive research, it has not yet been applied in clinical practice. The reason is safety concerns. This method can destroy not only cancer cells but also normal cells. Immune cells do not guarantee perfect accuracy when recognizing antigens, and artificially manipulated immune cells are particularly prone to causing problems. Nevertheless, since this method is faster and more reliable than existing methods that directly degrade telomerase, extensive research is currently underway.
Although cancer treatment research using telomeres is currently undergoing a process of trial and error, it is making new advancements and moving forward. In addition to telomeres, various other methods—such as treatments using viruses and light—are being researched, and there are projections that cancer will be completely conquered by around 2030 as a result of these efforts. Before long, patients may be freed from the suffering of cancer treatment, and the notion that cancer is an incurable disease may become a thing of the past.
