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Ελληνικά
Resistance of cancer stem cells to genotoxic insults is considered as one of the major causes of tumor recurrence, often resulting in enhanced aggression and poor prognosis of the median survival. Particularly, treated ER/PR and/or HER2 negative breast tumors present high rates of recurrence accompanied by frequent and varied metastases and short life expectancy.
The key objective of this proposal is a systematic analysis of the major underlying mechanisms responsible for the resistance of cancer stem cells to genotoxic damages caused by treatment schemes. These mechanisms are considered to include DNA repair mis-regulation as well as ROS inactivation.
At the outset of the project, the expression of DNA repair key molecules, representing major DNA repair pathways, will be examined in MCF7 derived cancer stem cells and CD44+/CD22-/lowALDH1+ breast cancer stem cells from patient biopsies (WP1, 2). The DNA repair capability of these cells will be further investigated at the gene expression and protein level (WP3). In parallel, cancer stem cells, isolated from patients, will be cultured in primary cultures and their intrinsic ability to effectively repair their genome will be examined (WP4). The obtained results will be evaluated in relation to at least a 4-year follow-up of patients and in correlation to the treatment protocols followed. Mono-and multiparametric statistical analysis will be additionally incorporated (WP5).
In conclusion, the proposal is expected to:
- further elucidate the mechanisms involved in DNA repair regulation,
- support the design of more effective personalized treatment protocols,
- promote prognosis of breast cancer progression,
- train young researchers and
- establish a core research network from various disciplines at National level with a potential to be expanded at European level.
Such a network would enable us to disseminate the results of our project in a more integrative manner with expected strong socio-economic benefits.
