Cancer : GTPases et suppresseurs de tumeurs.

Abstract

Le cancer est une maladie du fonctionnement même de nos cellules qui perdent le contrôle de leur prolifération, échappent à l’apoptose et deviennent immortelles. Elle résulte de la coopération entre l’activation d’oncogènes dominants et l’inactivation de gènes suppresseurs de tumeurs, processus qui sont amplifiés par le défaut des mécanismes assurant normalement la stabilité et l’intégrité du génome. La coopération entre ces différents mécanismes résulte en l’oncogenèse ; les bases moléculaires de cette coopération commencent à être établies.

Cancer is a multistep disease which is inherent to the very nature of the cellular machinery. It consists primarily in the loss of control of cellular proliferation, immortalisation, and finally invasion of other tissues by the fully malignant cells. Cells normally control their proliferation in response to specific signals that result in intracellular cascades of molecular events that involve molecular switches such as Ras family GTPases. Cancer results from the synergistic activation of dominant oncogenes, the products of many such genes are normally involved in the transduction of mitogenic signals, and inactivation of tumour suppressors, some of which are involved in cell cycle control. In addition, the maintenance of telomere length is required for the immortalisation of human epithelial cells. These mechanisms are amplified by the loss of cellular checkpoints ensuring the repair of damaged DNA, and stability of the genome. Full understanding of these defects, and the development of novel diagnostic as well as therapeutic anti cancer strategies based on molecular approaches will constitute one of the most formidable challenges of the beginning of the third millennium.