Project : Implication of translesion synthesis in the therapeutic resistance of cancer

We have shown that ectopic expression of Rad18 in human somatic cells is sufficient to constitutively activate translesion DNA synthesis and shut down the DDR, as observed in the early embryo (Figure 1). In these conditions cells shows acquired resistance to DNA damaging agents, including those currenlty used in the clinical, such as cisplatin. We have also observed a strong expression of Rad18 in cancer stem cells of the agressive brain tumor glioblastoma, a cancer that shows an extraordinary resistance to therapy. We are currently exploring the possiblity to use Rad18 as a novel target in the treatment of this cancer whose outcome is still very poor.

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Figure 1. Ectopic Rad18 expression in somatic mammalian cells is sufficient to induce spontaneous translesion synthesis nuclear focus formation.