Cancer is a leading cause of death in the western world, second only to cardiovascular disease, and is therefore a European public health problem of overwhelming human and economic significance. The incidence of cancer is set to increase substantially with demographic and possibly environmental influences playing a part. However, 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 imminent, it is now timely to initiate a major European co-ordinated effort to translate fundamental scientific knowledge about cancer into safer, more effective, therapies and improved early diagnostic procedures.
MOL CANCER MED is focused on a single group of highly promising anticancer targets associated with telomerase and telomere maintenance. Repression of telomerase in the somatic tissues of humans, and probably other long-lived mammals, appears to have evolved as a powerful protective barrier against cancer. Immortalization in vitro of normal human cells that lack telomerase involves the reactivation of telomerase or, rarely, an alternative (ALT) mechanism for maintaining telomeres. It is clear that telomerase is obligatory for continuous tumour cell proliferation, clonal evolution and malignant progression. Because telomerase is found in around 90% of human cancers and is essential for the continued proliferation (and clonal evolution) of cancer cells, it represents one of the most exciting anti-cancer targets thus far discovered. Results with a variety of telomerase inhibitory strategies in human cancer cells have confirmed that its functional inactivation results in progressive telomere shortening, leading to growth arrest and/or cell death through apoptosis. Promising candidate small molecule inhibitors are beginning to emerge that will form the basis for anti-telomerase drug development.
MOL CANCER MED is based on successful Framework 5 research concerned with establishing the value of the cellular immortality enzyme telomerase as an anti-cancer target (Project: QLG -1999- 01341; TACIT) and represents an expansion and elaboration of it. TACIT yielded results that have triggered new translational research with clearly defined clinical applications. To this set of activities have been added carefully selected new EU research teams, notably in the area of drug development.