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Developing Molecular Medicines for Cancer in the Post-Genome Era

Final Report Summary - MOL CANCER MED (Developing molecular medicines for cancer in the post-genome era)

Cancer is a European public health problem of overwhelming human and economic significance. There is now an improved molecular understanding of the key genetic, biochemical and cellular changes leading to cancer, in significant part due to the efforts of diverse groups of world-class EU-based scientists. With the completion of the human genome sequence it has now become realistically possible to support major European coordinated efforts to translate fundamental scientific knowledge about cancer into safer, more effective, therapies and improved early diagnostic procedures.

The cellular immortality enzyme telomerase (one of the most promising universal cancer markers) and associated telomere maintenance mechanisms, represent novel anti-cancer targets of enormous therapeutic and diagnostic potential. In MOL CANCER MED, a multinational EU translational cancer research consortium was established, in which talented cancer geneticists and molecular biologists worked in close collaboration with prominent pharmacologists, clinicians and pathologists to develop these exciting new cellular targets into measurable pre-clinical advances, within a four-year time-frame.

MOL CANCER MED was designed with the primary strategic aim of assembling the necessary critical mass of collaborating researchers engaged in telomerase, telomere and translational cancer research within the EU and, in doing so, promoting a far greater degree of scientific interaction than would have otherwise have been possible. The project was based upon a core group of seven institutions that collaborated very successfully in the Fifth Framework Programme (FP5) on a project aimed at evaluating the potential of telomerase as a cancer therapeutic target. This consortium was extended (to 14 institutions) in MOL CANCER MED to include experts in small molecule anti-cancer drug development targeted at cancer cell telomeres and telomerase.

Their results include:
(i) major advances were made in our understanding the value of telomerase, and known components of the telosome, as biomarkers for translational application in improving cancer diagnosis;
(ii) novel telomere-related molecular targets were identified and positively evaluated, e.g. hEST-1, TERRA, the POT1-TPP1 complex, TRF2, telomeric aggregates, telomerase hTERT repressor pathways and TLI cell growth-promoting functions of telomerase, that promise to be of value as anti-cancer drug targets and diagnosis of the common human cancers; and
(iii) a rich source of novel small molecule drug leads was generated, with a sub-set of these displaying highly promising anti-cancer properties in preclinical validation.