Because TMCG/DIPY treatment modulates the methy lation status this research and stability of E2F1, we observed that the 4OHT dependent overexpression of E2F1 positively influences E2F1 mediated cell death in ER negative breast cancer cells. Background Hepatocellular carcinoma is the third cause of cancer related death worldwide with an overall ratio of mortality to incidence of 0. 93. Due to the often late diagnosis, possible curative therapies such as hepatic re section, liver transplantation and percutaneous ablation can be offered to only a limited number of patients highlighting the need for the development of new treat ment strategies. Modern technologies have allowed the emergence of new techniques in the field of radiation ther apy.

For example, three dimensional conformal radiother apy has the potential to accurately deliver high doses of radiation within a well defined HCC tumor volume while sparing the surrounding non tumor liver parenchyma and the adjacent organs, therefore limiting radiation induced complications. This method has shown promising results with an 80% complete response for small size HCC nodules in patients non eligible for standard cura tive therapies. Molecules targeting DNA repair pathways have shown great potential to sensitize tumor cells to both chemo and radiotherapy and increase their cytotoxicity. In hibitors of poly polymerases fall into this category. Poly ation is carried out by several members of the PARP family, of which PARP 1 is the most prevalent.

This ubiquitous post translational modification in mammalian cells modulates many cellular responses including transcription, chromatin dynamics, differentiation and cell death, in addition to playing a key role in the response to DNA damage. Once activated, the PARP proteins catalyze the formation of ADP ribose polymers onto acceptor proteins. In addition to this direct covalent modification, some proteins have a high affinity for the polymers themselves and this is exploited in some settings, for instance in DNA repair, for the control of the localization and function of different repair proteins. The radiosensitization effects of PARP inhibitors have been shown to be specific to cells in the S phase of the cell cycle and are due to the collision of the persist ing single strand breaks with replication forks and the for mation of a lethal DNA double strand break.

This cell cycle specificity of the impact of PARPi could be of particular benefit in the treatment of cancer cells that often show radioresistance during the S phase of the cell cycle Brefeldin_A and PARPi might result in increased efficiency of radiotherapy in rapidly growing tumors with a high S phase content. Changes in the tumour micro environment brought about by PARPi can also have an impact on responses to radiotherapy.