Fighting Cancer by Inhibiting Telomerase

Finding new ways to improve cancer therapies has presented opportunities and challenges to biomedicine and biotechnology.  After learning that telomere length might serve as an effective predictor of cancer risk and survival, scientists have looked to these chromosomal ends for purposes that go beyond their use as signals of cell deterioration. By inhibiting telomerase, a protein that is reactivated when telomeres become too short, scientists had hoped to develop cancer therapies that are more effective in targeting malignant tumors while avoiding damaging harmless cells. However, a new study published online earlier this year found no significant correlation between telomere length and cancer risk. Instead, it suggests that cancer risk is influenced more by genetic variation in a telomerase gene than by the length of the telomere itself.

During each cycle of cell division, small portions at the ends of the chromosomes are lost upon DNA replication. Telomeres are comprised of repetitive sequences of bases that protect the ends of the chromosomes from the loss of essential genetic material. Once the telomere is shortened too much, however, DNA replication could eliminate the telomere entirely, leading to genomic instability and end-to-end fusions between chromosomal strands.1 If this happens, the cell is considered to be senescing, or deteriorating, and headed towards imminent death.  However, older cells with short telomeres are capable of activating proteins that can restore the length and lifetime of telomeres.2

The proteins that play a key role in restoring telomeres are called telomerase, and in normal, healthy cells their function is mostly limited to embryonic cells, adult male germ line cells, and stem cells. Telomerase activity must be regulated, and failure to regulate it properly can lead to uncontrolled cell division, which can lead to cancer, bone marrow disorders, and other diseases.1 Such failures in regulation are rare, but a cell that reactivates telomerase to recover lost telomere length might overcompensate, leading to uncontrolled cell division.2 Indeed, scientists have found that telomerase is up-regulated in 90% to 97% of ovarian cancers, but remains undetected in pre-malignant lesions. This suggests that telomerase is no longer inhibited when a cancer begins to form.3

Developing cancer therapies that inhibit telomerase, therefore, seems to be a promising approach, since it allows for combating cancerous cells while reducing harm caused to neighboring normal cells.1 Multiple studies have suggested that telomerase inhibition leads to accelerated telomere shortening, compromised tumor growth, and eventual cell death.4

For the most part, scientists have thought that telomere length is a key indicator of cancer risk. Indeed, studies have identified such links between telomere length and cancer mortality. Researchers “found a doubling of cancer mortality with every 1-SD decrease in telomere length.”2 As per these findings, it is hoped that telomere length could assist in future cancer-screening efforts by providing effective estimates of tumor prognoses.

A study released last January, however, demonstrates that telomere length is not necessarily a good indicator of cancer risk. After measuring the relative telomere lengths of New England women diagnosed with ovarian cancer, the researchers found no significant correlation between relative telomere length and ovarian cancer risk. Instead, they found a more statistically significant association between ovarian cancer risk and genetic variation in the TERT gene, which encodes part of telomerase.3

These findings contrast with other scientists’ understanding of telomeres and cancer, by showing that telomere length is not necessarily a clear indicator of cancer risk. Indeed, a study published in April by another group of researchers revealed a different conclusion — namely, an association between telomere length and ovarian cancer risk. Because such inconsistencies could result from differences in methodology, scientists continue to investigate this relationship.5 Such differences in methodology include study design, sample size, study population, and timing of chemotherapy. The researchers in both studies also suspect that chemotherapy’s influences on telomere length, along with other factors like smoking status or obesity, may have obscured the results of their study.  For example, samples collected soon after cancer diagnosis are likely to be influenced by chemotherapy, while samples collected much later are likely to be influenced by cancer survival. Ultimately, scientists have been unable to resolve these issues, and if anything, the results call to attention the need for further research in the relationship between telomeres and cancer therapy.3,5


  1. Sprouse, Alyssa A. et al. 2012. “Pharmaceutical regulation of telomerase and its clinical potential.” Journal of Cellular and Molecular Medicine 16, no. 1 (2012): 1-7. Accessed May 1, 2012. doi: 10.1111/j.1582-4934.2011.01460.x.
  2. Kelly, Janis C. “Short Telomeres Tied to Cancer Risk.” Medscape Medical News. WebMD. July 9, 2010. Accessed February 11, 2012.
  3. Terry, Kathryn L. et al. 2012. “Telomere Length and Genetic Variation in Telomere Maintenance Genes in Relation to Ovarian Cancer.” Cancer Epidemiology, Biomarkers and Prevention. Accessed May 1, 2012. doi: 10.1158/1055-9965.
  4. Blasco, Maria A. 2001. “Telomeres in Cancer Therapy.” Journal of Biomedicine and Biotechnology 1, no. 1 (2001): 3-4. Accessed May 1, 2012. doi: 10.11551/S1110724301000109.
  5. Martinez-Delgado, Beatriz et al. 2012. “Shorter telomere length is associated with increased ovarian cancer risk in both familial and sporadic cases.” Journal of Medical Genetics. Accessed May 1, 2012. doi: 10.1136/jmedgenet-2012-100807.
  6. Image credit (Creative Commons): Samulili. “Telomere.” Wikimedia Commons. Last modified March 12, 2005.
  7. Image credit (public domain): Padilla-Nash, Hesed and Thomas Ried. “Telomeres.” National Institute of General Medical Services. Last modified April 26, 2011.

Edgar Pal is a rising third-year student at the University of Chicago, and is the Executive Editor of The Triple Helix Online. Follow The Triple Helix Online on Twitter and join us on Facebook.

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  • I’m not a scientist or a medical expert but if my thoughts are worth anything, I would have thought it was obvious that telomere length would not corelate with uncontrolled cell division ie cancer. If telomeres are there to protect from loss of genetic data during cell division, it seems logical to me that the loss of that genetic data might be the cause in the first place, for cancer, not the telomeres. The increased telomere length if any might be secondary response to cancer but the original cause is loss or corruption of this genetic data. This is because the cells in being triggered into uncontrolled division initially become so shortened in there telomere length, that telomerase is then expressed in over abundance to try and increase the length of the canceris telomeres but the response is too late.