This year’s Nobel prize in Physiology or Medicine was awarded to Elizabeth Blackburn, her former student Carol Greider, and Jack Szostak for their discovery of “how chromosomes are protected by telomeres and the enzyme telomerase”. It is actually more than a quarter of a century since these recipients made the unique and important discovery that while every cell replication cycle results in a loss of DNA from the ends of the chromosomes, there are expendable telomeric sequences - long TTAGGG nucleotide repeats with an associated protein complex termed shelterin - present at the chromosome ends. Eventually, however, the progressive shortening that occurs at each cell division causes the telomeres to reach a critical length, resulting in cellular senescence and death. In stem cells and germ-line cells telomere length is maintained by the action of telomerase, but this enzyme is not expressed in normal somatic cells.
The trend over recent years has been for such important work to be rewarded in a more timely fashion, so why did the prize for the work on telomeres and telomerase buck the current trend? Before a discovery is rewarded by the Nobel Committee it must not only be identified as ‘solid and correct’, but it must be relevant and of lasting medical importance. The potential medical applications of this work may not have been evident twenty-five years ago; possibly the plethora of articles in the popular press with headlines such as ‘Elixir of eternal youth discovered’ trivialised the importance of the discovery. And the absurd claims by makers of telomerase-containing cosmetics that applying their face cream to the dead cells of the stratum corneum would “convert resting adult cells to newly minted skin cells” may not have helped either. However numerous studies have now demonstrated the importance of telomerase as both a biomarker and a potential
therapeutic drug target in oncology.
Cancer cells are, of course, able to proliferate indefinitely, and carcinogenesis is associated with telomerase reactivation in somatic cells. Telomerase activity has been demonstrated in extracts from many types of cancer, including lung, breast, colorectal, prostate and liver cancers, as well as oral carcinomas and neuroblastomas. The enzyme is thus an excellent biomarker for both cancer diagnosis and prognosis in most tissue types. Several methods have been developed in order to assess telomerase activity, although further work is needed to find a method which is both simple and precise. And in the drug discovery field, because cancer cells require telomerase in order to continue dividing unchecked, compounds which inhibit telomerase expression should inhibit tumour cell division. Several clinical trials involving anti-telomerase therapeutics have already been initiated.
The discovery of telomeres and telomerase will surely enable more effective diagnosis, prognosis and treatment of cancer. As required by the Nobel Committee, these benefits are indeed likely to be of lasting medical importance.