Telomeres and Cancer

Telomeres are structures found at the ends of human chromosomes that contain thousands of repeats of repetitive TTAGGG DNA sequences. A ribonucleoprotein enzyme complex known as telomerase maintains telomere length in cancer cells by adding TTAGGG repeats onto the telomeric ends, compensating for the normal shortening of telomeres in all dividing cells.

The theory that telomerase is the culprit in maintaining human cancers was proposed in 1990, but the evidence just recently became persuasive enough. A majority of human cancers exhibit critically short telomeres, suggesting that tumors can arise from genetically instable cells with dysfunctional telomeres.

Molecular mechanisms of cancer initiation

Most human cancers that arise during ageing and at the end stage of different chronic diseases are associated with increased rates of chromosomal instability, which can induce genetic lesions responsible for the step-wise progression of altered cells into malignant, cancer cells.

Since telomere shortening is strongly correlated with an increased risk of cancer during aging and chronic disease, the scientific literature suggests that the loss of telomere capping function contributes to the induction of chromosomal instability and cancer initiation process.

In addition to its role in initiating chromosomal instability, telomere dysfunction gives rise to cancer by inducing environmental alteration. In vitro evidence has shown that shorter telomeres directly contribute to the swift progression of the earliest stages of certain malignancies.

The activation of telomerase represents the most common pathway for stabilizing telomeres in human cancers. In addition to this, an improvement in telomere capping function allows proliferation and survival of malignant cells with critically short telomeres.

Different research groups have demonstrated an altered expression of telomere-binding proteins in human cancer in comparison to non-transformed cells and tissues. 10-20% of malignant tumors in humans do not express telomerase, but stabilize telomeres by an alternative mechanism of telomere elongation.

Targeting telomerase for cancer therapy

Ideal cancer therapeutic targets are those that are specific for certain tumors and that pose a threat for maintaining its malignancy. As a role of telomerase in the unlimited proliferative potential of cells has been repeatedly demonstrated, it has been proposed as a potential anticancer target.

In essence, the idea seems exciting, as telomerase is found in different types of human cancers, while at the same time absent from many normal cells. Thus specific agents that would target telomerase might kill malignant cells without altering the function of a majority of normal cells in our body. Additionally, this approach could work for a wide array of cancers that contain telomerase.

Nevertheless, certain questions need answers if we are to add telomerase inhibitors to our armamentarium of drugs against cancer. Assessing the importance of telomerase for normal cells or demonstrating that its inhibition can in fact destroy telomerase-producing cancers (and supersede telomere-salvaging pathways) are just a couple of examples.

Therefore additional research is definitely required in order to further establish the exact roles of telomeres and telomerase in the biology of cancer stem cells, which will likely contribute to success of novel therapeutic approaches against different types of malignant diseases.


  6. Hiyama K, Hiyama E, Tanimoto K, Nishiyama M. Role of Telomeres and Telomerase in Cancer. In: Hiyama K, editor. Telomeres and Telomerase in Cancer. Springer Science + Business Media, LLC 2009; pp. 171-180.

Further Reading

Last Updated: Nov 19, 2015


  1. Vadim Shapoval Vadim Shapoval Ukraine says:

    Telomeres (the specific DNA-protein structures) found at both ends of each chromosome, protect genome from nucleolytic degradation, unnecessary recombination, repair, and interchromosomal fusion. Telomere length decreases with age. Certain individuals may be born with shorter telomeres or may have genetic disorder leading to shorter telomeres. Telomeres are created by telomerases. Several studies indicate that shorter telomeres are a risk factor for cancer. Shorter telomeres can induce genomic instability. Telomerases (ribonucleoprotein enzymes) are reactivated in most cancerous immortalized cells. Lysosomal alterations are common in cancerous cells. Lysosomes control cell death at several levels. Defects in cellular iron metabolism can cause the Warburg effect. Many cancerous cells are considered immortal because telomerase activity and lysosomal alterations allows them to divide virtually forever. However, subsets of immortalized cells lack telomerase activity. Iron is an essential cellular nutrient that is critical for DNA synthesis (for many cellular processes). Ribonucleotide reductase is an iron-dependent enzyme that is required for DNA synthesis. Iron is so important that without it all life would cease to exist. In human cells, iron is an essential component of hundreds of proteins and enzymes. Heme is an iron-containing compound found in a number of biologically important molecules. Cytochromes are heme-containing (and iron-containing) compounds that have important roles in mitochondrial electron transport. Nonheme iron-containing enzymes are also critical to energy metabolism. Iron Response Elements are short sequences of nucleotides found in the messenger RNA (mRNA). Several genetic disorders and all known human carcinogens may lead to pathological accumulation of iron in the cells. While iron is an essential mineral, it is potentially carcinogenic. The presence of excessive iron inside cancerous cells can lead to telomere end-replication problems, lysosomal alterations, mitochondrial dysfunction (Warburg effect), DNA mutations, chromosomal abnormalities (deletions, duplications, inversions, ring formations, translocations), chromothripsis and mitotic catastrophes. Primary tumors always develop at body sites of excessive iron deposits.

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