How do telomeres and telomerase relate to cancer development?

Telomeres are repetitive DNA sequences located at the ends of chromosomes that act as protective caps to maintain chromosome stability and prevent degradation. Telomerase is an enzyme that helps maintain telomere length by adding telomere repeat sequences to the ends of chromosomes. In normal cells, telomerase is not expressed or is expressed at low levels, leading to telomere shortening with each cell division. When telomeres become critically short, cells enter a state of replicative senescence or undergo apoptosis to prevent the propagation of damaged or abnormal cells.

Cancer cells, on the other hand, have a unique ability to maintain telomere length despite extensive replication. They achieve this through the activation of telomerase or alternative lengthening of telomeres (ALT) pathways. Telomerase is activated in approximately 90% of all cancers, and the expression of the telomerase gene is often upregulated to maintain telomere length and support cell immortalization. In the remaining 10% of cancers, telomerase is not activated, but ALT mechanisms allow for the maintenance of telomere length.

While telomerase activation and telomere length maintenance are critical for cancer cell survival and proliferation, they also present potential targets for cancer therapy. Telomerase inhibitors, which block telomerase activity, have been investigated as potential anticancer agents. These agents have shown promising results in preclinical studies and are currently being evaluated in clinical trials.

However, the use of telomerase inhibitors as cancer therapy is not without its challenges. Since telomerase activity is also essential for the maintenance of telomere length in normal stem cells, telomerase inhibition could also result in unintended side effects such as stem cell depletion and tissue dysfunction. Additionally, the use of telomerase inhibitors may select for cancer cells that have acquired ALT mechanisms for telomere maintenance, making the therapy ineffective in the long run. Therefore, the development of more specific and targeted approaches for inhibiting telomerase activity or ALT mechanisms remains an active area of research in cancer biology.