In this blog post, we explore the scientific mechanisms and latest trends in therapeutic research regarding how telomeres enable the infinite division of cancer cells while also influencing human aging.
A clue to unlocking the long-unresolved secrets of aging has recently been discovered: telomeres. While telomeres are suspected to cause aging, harnessing them could conversely offer hope for conquering aging. Meanwhile, telomeres also exist in cancer, one of the most deadly diseases threatening human health. Yet, the telomeres that cause human aging exhibit a completely different response in cancer cells. In cancer cells, telomeres do not accelerate cellular aging. This article will explore what telomeres are, what the peculiar reaction occurring in cancer cells is and why it happens, and also examine efforts to harness this to combat cancer.
Telomeres refer to specific nucleotide sequences that repeat at the ends of DNA strands to compensate for base loss during DNA replication. Our bodies constantly grow, heal wounds, and maintain organ function through cell division. During this process, DNA is always replicated to ensure identical DNA enters the two divided cells. However, due to functional issues with enzymes during DNA replication, an imbalance occurs where one strand of DNA becomes shorter. This means that with repeated cell division, the DNA strands gradually shorten, posing a risk of damage to genetic information. To defend against this, strands called telomeres exist at the ends of DNA. These telomeres are strands composed of repetitive, seemingly meaningless nucleotide sequences that protect against damage to vital genetic information. However, as cell division continues, these telomeres eventually become completely depleted. Consequently, many scientists believe the secret to aging lies within these telomeres and are conducting research accordingly.
In contrast, cancer cells exhibit a different phenomenon. Cancer is a disease where the regulatory mechanisms that normally limit cell growth fail to function properly. Cells typically communicate 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 occurs to repair the damaged tissue. However, cancer cells have impaired regulatory mechanisms and divide continuously.
A crucial 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. These cells continue dividing to this day and are used in numerous research studies. So why aren’t cancer cells affected by the problem of progressively shortening DNA ends? The answer lies in an enzyme called telomerase. This enzyme primarily functions during the formation of germ cells. Germ cells are produced through meiosis; when male and female germ cells meet and fertilization occurs, a zygote is formed, which then develops into a baby. During meiosis, genetic information remains unchanged, so germ cells retain the exact genetic information of the somatic cell where meiosis first occurred. However, somatic cells may already have shortened telomeres. Telomerase is the solution to this problem.
Telomerase acts as a reverse transcriptase enzyme, lengthening 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. Typically, this enzyme is inactive in somatic cells but becomes active during the production of germ cells. However, most cancer cells utilize telomerase to extend their lifespan indefinitely. Research indicates that telomerase is abnormally activated in most cancers. Thanks to this enzyme, cancer cells can divide endlessly while maintaining a structure where telomeres do not shorten.
Theoretically, developing drugs that reduce or eliminate telomerase activity within cancer cells could conquer cancer. However, reality is not that simple. First, telomeres can regenerate through other means even without telomerase. For example, methods like homologous recombination and DNA repair exist. These methods can extend DNA length or increase telomere length. Another problem is that even if telomere synthesis is blocked, it takes time for telomeres to be completely depleted. During this time, cancer cells can continue dividing, making it difficult to take appropriate action in the meantime.
Conquering cancer is not a problem that can be solved simply, so researchers continue studying telomere-related cancer therapies. Since abnormal telomerase activity is found in about 90% of cancers, it could be a crucial clue for cancer control. One approach involves removing telomerase and then using the immune system to completely eliminate cancer cells. This method involves applying proteolytic enzymes to cancer cells to break down telomerase. The resulting fragments then attach to the cancer cell surface, acting as antigens. Immune cells recognize these antigens and are induced to attack the cancer cells.
Although this therapy has been 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 problems. Nevertheless, this method is faster and more effective than the existing direct telomerase degradation method, leading to extensive ongoing research.
Thus, while telomere-based cancer treatment research faces trial and error, it advances through new developments in the process. Beyond telomeres, various methods like viral and light-based therapies are being studied. These efforts have led to projections that cancer could be completely conquered around 2030. Soon, patients may be freed from the suffering of anticancer treatments, and the notion of cancer as an incurable disease could become a thing of the past.