Final Activity Report Summary - ABC TRANSPORTERS (Implementation of a pharmacogenomic approach to predict ABC transporter substrates and compounds selectively targeting multidrug resistant cancer)
The major challenge of the post genomic era is to analyse 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. 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, referred to as 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. The major aim of this project was to apply a pharmacogenomic approach to discover ABC transporter substrates and MDR1-inverse compounds that selectively killed multidrug resistant cancer cells. The results could be summarised as follows:
1. we delineated defining features of candidate ABC transporter substrates,
2. we proposed a mechanism of action for the toxicity of newly identified MDR1-inverse compounds and
3. we developed models and transport assays for the study of drug-transporter interactions.
ATP-binding cassette (ABC) proteins comprise the largest protein family, many members of which are of immediate medical importance and relevant to human health. The major aim of this project was to apply a pharmacogenomic approach to discover ABC transporter substrates and MDR1-inverse compounds that selectively killed multidrug resistant cancer cells. The results could be summarised as follows:
1. we delineated defining features of candidate ABC transporter substrates,
2. we proposed a mechanism of action for the toxicity of newly identified MDR1-inverse compounds and
3. we developed models and transport assays for the study of drug-transporter interactions.