Metabolism is a well-known factor of a drug's pharmacological effect as it impacts the drug-target interaction with respect to time and concentration. As a result, studies aimed at understanding a compound’s metabolic stability and identification of enzymes/transporters responsible for metabolism are key in drug discovery and development. Prediction of likely clinical scenarios due to metabolism/transport involves integration of the metabolic stability/enzyme/transporter information with known factors that may in turn affect the activities of the enzymes; such as induction, inhibition or genetics (genetic polymorphisms). For anti-cancer drugs, further modification of drug metabolism may be target-mediated - modulation of a target signalling pathway may up- or down-regulate the expression of a transporter/drug metabolising enzyme. Prediction of the likely impact of drug-target interaction on metabolism in this case, is not easy and may be confounded by altered drug metabolism capacity due to the disease which may only be observed after multiple administration of the compound in the clinic.
The overall aim is to build a better understanding of the contribution and significance of signalling pathways of interest to the expression levels of drug metabolising enzymes/transporters and how these can, in turn, be modified when dysregulated in cancer. In addition, the impact of drugs targeting these pathways would be of particular interest.
We would welcome studies on:
1. The impact of dysregulated signalling pathways on expression of drug metabolising enzymes and transporters
2. The effect of signalling pathways on drug pharmacokinetics
3. In vivo studies in patients demonstrating possible modification of drug pharmacokinetics due to disease-altered drug metabolism capacity
4. Gene expression studies that impact on patients response to anti-cancer drugs
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
Metabolism is a well-known factor of a drug's pharmacological effect as it impacts the drug-target interaction with respect to time and concentration. As a result, studies aimed at understanding a compound’s metabolic stability and identification of enzymes/transporters responsible for metabolism are key in drug discovery and development. Prediction of likely clinical scenarios due to metabolism/transport involves integration of the metabolic stability/enzyme/transporter information with known factors that may in turn affect the activities of the enzymes; such as induction, inhibition or genetics (genetic polymorphisms). For anti-cancer drugs, further modification of drug metabolism may be target-mediated - modulation of a target signalling pathway may up- or down-regulate the expression of a transporter/drug metabolising enzyme. Prediction of the likely impact of drug-target interaction on metabolism in this case, is not easy and may be confounded by altered drug metabolism capacity due to the disease which may only be observed after multiple administration of the compound in the clinic.
The overall aim is to build a better understanding of the contribution and significance of signalling pathways of interest to the expression levels of drug metabolising enzymes/transporters and how these can, in turn, be modified when dysregulated in cancer. In addition, the impact of drugs targeting these pathways would be of particular interest.
We would welcome studies on:
1. The impact of dysregulated signalling pathways on expression of drug metabolising enzymes and transporters
2. The effect of signalling pathways on drug pharmacokinetics
3. In vivo studies in patients demonstrating possible modification of drug pharmacokinetics due to disease-altered drug metabolism capacity
4. Gene expression studies that impact on patients response to anti-cancer drugs
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
