Telomere biology: Rationale for diagnostics and therapeutics in cancer

Abstract

The key step of carcinogenesis is the malignant transformation which is fundamentally a telomere biology dysfunction permitting cells to bypass the Hayflick limit and to divide indefinitely and uncontrollably. Thus all partners and structures involved in normal and abnormal telomere maintenance, protection and lengthening can be considered as potential anti-cancer therapeutic targets. In this Point of View we discuss, highlight and provide new perspectives from the current knowledge and understanding to position the different aspects of telomere biology and dysfunction as diagnostic, preventive and curative tools in the field of cancer.

Keywords: alternative lengthening of telomere; cancer diagnostics; cancer therapeutics; shelterin; telomerase; telomere; telomere uncapping.

Figure 1.

(A) Telomere length as a function of cell division in normal and tumor cells. When the telomere length reaches a critically short length cells enter into senescence (Hayflick Limit). Cancer cells acquire alterations allowing telomere maintenance and indefinite cell proliferation. Telomere biology hallmarks (B–G, I–J) that could be monitored, that are implicated in telomere protection, or in telomere lengthening (highlighted in gray) and that could be used as diagnostic tools (blue boxes), as targets for treatment (red boxes) and the prevention of relapse (yellow box) are indicated. (H) Schematic representation of the evolution of the disease over time with an arbitrary color code reflecting acuteness of the disease (bottom) and the increase in lengthening activity that permits diagnosis and detection of relapse.