Objectif
"The chemotherapeutic drugs cisplatin and paclitaxel are used in the treatment of ovarian cancer. However, the rate of relapse after therapy is high and is often due to the development of drug resistance. Drug-resistant cancer cell lines in the laboratory frequently have an inverse resistance relationship between cisplatin and paclitaxel. When cisplatin resistance occurs, cells are likely to have no change in resistance to paclitaxel and some cells even become more sensitive to paclitaxel. There is also clinical evidence to support the benefit of alternating between cisplatin and paclitaxel therapy in ovarian cancer. The aim of this project is to understand the molecular mechanism of inverse-resistance by identifying genes and proteins associated with the resistance phenotype in a panel of drug-resistant cancer cell lines. One gene which we have associated with the mechanism of inverse-resistance by literature search is BRCA1. This project has three phases 1) Genomic and proteomic profiling of a panel of drug-resistant cell lines; 2) Functional validation of identified targets and understanding of the mechanism of inverse resistance and 3) Investigation of the role of BRCA1 in the inverse-resistance relationship between cisplatin and paclitaxel. Validated molecular markers associated with the inverse-resistance relationship could potentially be used as a clinical test to determine if an individual patient is likely to be resistant to cisplatin or paclitaxel therapy. Patients likely to respond to cisplatin or paclitaxel could be given the appropriate drug, while patients unlikely to respond to either can be given alternative chemotherapy."
Champ scientifique
Appel à propositions
FP7-PEOPLE-2010-RG
Voir d’autres projets de cet appel
Régime de financement
MC-ERG - European Re-integration Grants (ERG)Coordinateur
D02 CX56 DUBLIN 2
Irlande