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Development of Prostate Cancer gene therapy : A collaborative network


Prostate cancer is ubiquitous world-wide and since the tumour is associated with the ageing process, it is clearly a growing health problem in Europe. At present we have no method of predicting those patients at risk of developing malignant decease, and no consistent genetic markers have been identified. Also, no treatment has proven to be efficient as soon as the tumour become invasive. It is therefore of some importance to design a new therapeutically approach using cellular and molecular biology tools. A major break through may come from the development of a tissue specific transfer strategy of 'suicide' genes as a gene therapy. This approach may allow the treatment of (I) primary cancer which is conventionally treated by surgery allowing a better recovery in term of impotency and urinary incontinence, and (ii) distant metastasis for which no treatment is effective. Indeed, the specific targeting of prostate cells should render metastases accessible to therapy for the first time in prostate cancer. Therefore, we have set out to develop a joint research effort within the European Union and 7 partners from France, GB, Ireland, Belgium and Italy have accepted to join the network. We believe that such a task force should rapidly establish a leadership in the field where a world-wide competition is developing. Also, one of the major aims of this research effort is to allow rapid transfer to the clinic, with industrial partnership.

Three stages are involved in development of human gene therapy and different possibilities are available in view of the complementary expertise of the partners associated with the network. (i) The transduction by viral vectors or transfection by DNA-mediated systems of appropriate target cells are tools which can be adapted for use by selection of properties useful in particular situations. Retroviruses and adenoviruses are among those which have been the most widely used. (ii) By enhancement of prostate-specific gene expression, in addition to a specificity of gene delivery, we can eliminate aberrant expression of therapeutic genes in non-prostatic target cells. For this we are developing a set of prostate specific promoters able to drive expression of effector genes. (iii) The feasibility assessment of different effector genes to direct 'suicide' or proliferation control of the targeted prostate cancer cells has prompted us to design parallel strategies to maximise the complementary expertise's of the network partners. Thus, we have focused on gene products which are cytotoxic, regulate apoptosis or inhibit proliferation. To test these alternatives, standardised in vitro and in vivo models are already available or are under development within the network.

As a result, we expect to improve the quality of the cellular and molecular research carried out on prostate cancer with the objectives of gaining new insights in diagnosis and treatment. By providing a new approach to treat prostate cancer, it should assist in a significant improvement for both the patient and the social budget.

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Hôpital Saint-Louis
1,rue claude vellefaux
75475 Paris

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