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It is well recognised that upregulation/reactivation of telomerase, the telomere-lengthen‐ ing enzyme, is the sine qua non of cellular immortalisation and malignant transformation. But there is also convincing evidence that telomerase stands at a crossroads where several developmental signalling pathways meet and that its upregulation/reactivation has ef‐ fects beyond maintaining telomere length, such as altering energy metabolism and mod‐ ulating gene expression. We believe that it is important to realise that, in a pathological context, such extratelomeric effects of telomerase are related to the emergence and persis‐ tence of the cancer stem cell (CSC) phenotype. Given the common conception of cancer stemness as a major contributor to therapy resistance and tumour relapse, a more com‐ plete annotation of biological mechanisms for its regulation by telomerase will provide the opportunity to develop telomerase-targeted anticancer therapies which kill or differ‐ entiate CSCs effectively.

On the Far Side of Telomeres: The Many Roles of Telomerase in the Acquisition and Retention of Cancer Stemness