Research Topic

Improving cancer chemotherapy through pharmacogenomics

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It is well known that the efficacy and safety of chemotherapeutic drugs show substantial variability which can be explained, to a great extent, by genetic factors. Polymorphism of genes encoding drug-metabolizing enzymes, drug transporters and drug targets influences the pharmacokinetics and pharmacodynamics ...

It is well known that the efficacy and safety of chemotherapeutic drugs show substantial variability which can be explained, to a great extent, by genetic factors. Polymorphism of genes encoding drug-metabolizing enzymes, drug transporters and drug targets influences the pharmacokinetics and pharmacodynamics of anticancer drugs. Several chemotherapeutic agents are often more harmful to normal tissues than the targeted tumor, giving rise to tumor cell resistance, toxicity and occasionally secondary neoplasia. Accordingly, current practices for the dosing of therapeutic agents should be improved through the understanding of gene variation associated with “drug life” inside the body. In order to be able to predict patient’s predispositions to treatment complications and poor outcome, it is essential to examine all candidate loci influencing response to the chemotherapeutic agents. Therefore, we also should gain better understanding of the metabolic pathways for activation or inactivation of these drugs, the interaction between drugs, age and gender sensitivities, and the impact of ethnicity and environmental factors so as to enhance effectiveness and/or reduce toxicity of the treatment.
A more rational use of expensive treatment drugs together with actions to minimize patient toxic events and its consequences would dramatically reduce medical costs, as an added benefit.
Pharmacogenomics is an emerging field focused on genetic variations relevant to drug action. The idea is that solid data about allele variants, haplotypes and their effects on gene expression, applied to the (dynamics of) chemotherapy regimens’ design and dosing, will prevent undertreatment while avoiding associated toxicity in patients. Some of the potential polymorphic target genes include CYP isozymes, transferases, dehydrogenases, deaminases, reductases, ABC transporters, drug receptors and DNA repair enzymes.
With this Research Topic we would like to present an updated overview of the current trends in the experimental genetic approaches worldwide and discuss future directions in cancer pharmacotherapy. Thus, we encourage authors to submit original experimental research work, regular and systematic reviews, opinion letters, and methods of modeling and simulation of pharmacotherapeutic response to cancer treatment with molecular approaches.
In summary, we strongly believe that this Research Topic could be a powerful tool for better understanding genetic basis of individual differences in patient’s response to antineoplastic drugs. The main scope of this issue is to gather evidence to conceive chemotherapy for clinical practice as a “tailor-made-suit” for each patient.


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