Telomeric Ends and Telomerase-Canonical and Non-Canonical Roles in Breast Cancer Tumorigenesis and Therapy Resistance

Telomerase is known as a very specific marker of embryonic cells. It is responsible for telomere elongation (bypassing the end-replication problem) and thus supports normal cell division during tissue and organ development. But it is generally absent or very low in most normal adult somatic cells. However, its overexpression in adulthood (due to secondary expression and activity restoration) is commonly known to be associated with cancer. Apart from its canonical function (associated with telomere length restoration), it also carries out various other roles. Its non-canonical activity covers mitochondrial and epigenetic processes. Consequently, it contributes to the cell response to stress and chemotherapeutic drug treatment. A more detailed understanding of these phenomena offers the opportunity to identify new pathways and targets that may serve as critical factors in breast cancer diagnostics and therapy. In this article, we summarize the latest reports on the discovery of telomerase's nature, including its canonical and non-canonical roles. The manuscript highlights how these mechanisms contribute to tumorigenesis, therapy resistance, and the survival of cancer cells. Understanding these multifaceted mechanisms behind hTERT's role in (breast) cancer progression and therapy resistance is crucial for developing more effective therapeutic strategies.