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Identification and characterization of novel human telomere-related biomarkers that aid cancer management by improving patient diagnosis, treatment selection, response monitoring, and drug development

Final Report Summary - TELOMARKER (Identification and characterisation of novel human telomere-related biomarkers that aid cancer management (...))

TELOMARKER was founded on a rapidly advancing molecular understanding of the deoxyribonucleic acid (DNA) protein structure of the human telomere and how this, together with the telomere-maintenance enzyme telomerase, was critically involved in the induction of cellular immortality, genomic instability and the clonal evolution of cancer. Thus, both dysregulated telomerase and cancer specific telomere dysfunction became extremely attractive human cancer biomarkers of enormous clinical potential, both for the development of novel diagnostic tools and in the identification and exploitation of new anti-cancer drug targets.

The primary objective was to bring together all relevant world leading expertise in mammalian telomere research within the European Union, in order to characterise panels of new and existing biomarkers of telomere function and dysfunction that might have clinical value, as well as to conduct an extensive preclinical evaluation of these biomarkers in human cancer cells and tissue samples and in transgenic and knockout mouse model systems.

The project consortium advanced knowledge of comparative telomere and telomerase biology in normal and malignant human cells and tissues, as well as in model systems that had telomere dysfunction, abnormally expressed telosomal proteins, or repressed telomerase. At the conclusion of the project the consortium had:

1. built a detailed understanding of the effects of quantitative differences in the known components of the telosome and their effects on telomere dysfunction in model systems
2. identified and characterised new factors influencing telomere maintenance, including biomarkers associated with recruitment of telomerase to the telomere and the transcriptional repression and de-repression of telomerase hTERT in normal and cancer cells respectively
3. advanced biomarker assays to the point that they could be developed into clinical laboratory test protocols
4. developed new anticancer drug screening systems and identified novel telomerase inhibitors
5. applied the new screens to identify novel signalling events downstream of telomere uncapping, as a prelude to pinpointing further key biomarkers of telomere dysfunction, and
6. preclinically validated promising cancer biomarkers, including telomere length, emerging from this work in extensive human tissue biobank studies.

The final results and trajectory of TELOMARKER were therefore wholly consistent with the original aims and objectives of the project. The vast majority of the project milestones and deliverables were achieved.

TELOMARKER proved to be highly competitive and was anticipated to have impact on an international scale. Cancer is a leading cause of death in the western world, second only to cardiovascular disease. Effective strategies to combat cancer are therefore urgently needed. TELOMARKER was intended to make a significant contribution in this direction and succeeded in its planned outcomes. The project deliverables were of a high impact nature, like the new biomarkers and protocols for cancer diagnosis and prognostic evaluation, new anti-cancer drug targets and ultimately new drug leads. The translation of this new knowledge from TELOMARKER into improved cancer diagnosis and treatment was expected to have a significant, measurable impact on the health and well being of European Union citizens.