Alexander Stuart, Bokai Zhang, Dirk Hockemeyer, Titia de Lange
Recent studies have shown that telomere attrition functions as a powerful and broadly effective tumour-suppressor mechanism that halts emerging cancers when telomeric DNA becomes depleted. This Review highlights new insights into how telomere attrition guards against cancer, including its role in limiting cell proliferation, the importance of telomere length at birth for lifelong cancer prevention, the mechanisms governing telomere length regulation and how telomerase activation enables malignant cells to bypass this barrier. In contrast to the popular perception that telomere shortening is harmful, the findings demonstrate that normal telomere attrition limits the risk of cancer and suggest that counteracting telomere attrition in healthy individuals (for example, by activating telomerase) could enable tumour outgrowth. Thus, such interventions are best reserved for patients with diseases caused by excessively short telomeres. The new data also further underscore the promise of telomerase inhibition as a broadly effective cancer therapy.