Grant: Master's Award: Canada Graduate Scholarships

VR23, an anti-cancer compound as a proteasome inhibitor has different sites of action in cancer cells, like NFkB, cell cycle, regulation of apoptosis, p53… through many of these mechanisms cancer cells could be more sensitive to the effects of radiotherapy, even in radio-resistance cell lines. p53 is often inactivated in malignant cells, as an example Proteasome inhibition results in accumulation of p53 and activation of p53 downstream target genes. As we know in severe DNA damage, like damage due to radiation therapy, p53 will lead to apoptosis and cell death. Activation of P53 will radiosensitize cancer cells as well. The hypothesis is VR23 may have synergy effects with radiation therapy. So the combination therapy in certain doses and interval could lead to dose reduction of both and same or more effects. Material and Methods: as drugs has specific effects we will test a variety of cell lines to test and monitory every single possibility. Data of cell survival from tests like: Sulforhodamine B colorimetric assay for cytotoxicity screening and clonogenic cell survival assay, will obtain for ranges of radiation doses, drug doses and drug in combination with radiation doses. Doses and intervals between radiation and drug and more importantly the order of radiation and drug will be monitored. From these data we could target specific spots. Next step is the assessment of molecular mechanisms underlying any special effects of this combinational therapy. Methods we will use are flow cytometry, confocal microscopy and western blotting.