Obiettivo Although considerable progress has been made in treating cancer over the past decade, there are still over 8 million deaths annually from cancer worldwide. Despite considerable advances in drug discovery, resistance to chemotherapy confounds the effective treatment of cancer patients. Cancer cells can become resistant to a single drug or they may acquire broad cross-resistance to mechanistically and structurally unrelated drugs (multidrug resistance (MDR)). ATP-Binding Cassette (ABC) proteins comprise the largest protein family, many members of which are of immediate medical importance and relevant to human health. In particular, ABCB1 (MDR1-Pgp) actively extrudes many types of drugs from cancer cells, thereby conferring resistance to those agents. Thus, innate or acquired expression of P-gp is a major problem in cancer chemotherapy. The major challenge of the postgenomic era is to analyze vast amounts of data. In this context, the application of pharmacogenetics has the potential to improve the management of patients, particularly by providing the molecular basis for choosing among the increasing number of chemotherapeutic agents available for the treatment.The basic hypothesis of this proposal is that a pharmacogenomic approach can be exploited to discover MDR1-inverse compounds that selectively kill multidrug resistant cancer cells. The proposed research utilizes a complex array of methodological tools that involves diverse state of the art techniques, such as chemoinformatic algorithms, a custom-made microarray, and biochemical assays for measuring and characterizing transport. Accomplishing the outlined aims will provide the foundation for the detailed and comprehensive framework to verify the viability of the presented hypothesis. Together, the aims help in determining the mechanism of action of MDR1-inverse compounds, setting the stage for a fresh therapeutic approach that may eventually translate into improved patient care. Campo scientifico medical and health sciencesbasic medicinepharmacology and pharmacydrug discoverynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicineoncologymedical and health sciencesbasic medicinepharmacology and pharmacydrug resistancemultidrug resistance Parole chiave ABC transporters MDR1 P-glycoprotein cancer chemotherapy multidrug resistance Programma(i) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Argomento(i) MOBILITY-4.2 - Marie Curie International Reintegration Grants (IRG) Invito a presentare proposte FP6-2004-MOBILITY-12 Vedi altri progetti per questo bando Meccanismo di finanziamento IRG - Marie Curie actions-International re-integration grants Coordinatore INSTITUTE OF ENZYMOLOGY, BIOLOGICAL RESEARCH CENTER, HUNGARIAN ACADEMY OF SCIENCES Contributo UE Nessun dato Indirizzo Karolina 29 BUDAPEST Ungheria Mostra sulla mappa Collegamenti Sito web Opens in new window Costo totale Nessun dato
