Riassunto analitico
The human genome sequencing has recently led to a real revolution in medicine. The post-genomic era is characterized by a new phase of biomedical research, which pays particular attention to two pharmacological disciplines known as pharmacogenetics and pharmacogenomics. Pharmacogenetics studies the individual variation in the DNA sequence (polymorphisms) in relation to drug response. One practical application of pharmacogenetics research consists in the possibility of predicting a patient's response to a certain drug on the basis of a genetic test, making it possible a tailored therapy ("the right drug at right patient"). Pharmacogenomics, studying interactions between genes, metabolic pathways and protein networks, tries to identify how both new and old drugs can interact in these networks.
It’s well known that response to xenobiotics can be very diverse in terms of failure or partial effectiveness and appearance of side effects, even making harmful to some individuals a compound otherwise harmless or benefic for others. The promise of pharmacogenetics and pharmacogenomics is to determine tolerance and responsiveness to a given drug, thus allowing the identification of the active compounds that appear to be more effective in each single patient for specific disease treatment.
For what concerns breast cancer, it encompasses a broad variety of diseases, that differ in terms of prognosis and response to therapeutic treatment. Determining such differences lead to a better diagnosis and prognosis prediction, and allows the design of a more targeted and personalized drug treatment, improving its effectiveness and reducing the risk and extent of side effects. The study of gene expression profiles of individual carcinomas at the time of clinical diagnosis was then inserted with this aim in two sets of therapeutic experimental protocols on using the drug Lapatinib (GW572016). The study was carried out using the Affymetrix GeneChip platform.
Microarray technology is one of the most powerful and flexible tools of the post-genomic era and makes it possible to collect information on thousands of genes, drawing an overall picture of gene expression. The whole of genes transcribed from genomic DNA is called "expression profile" or transcriptome and defines the molecular phenotype of a cell and therefore its functions. In contrast to genome, transcriptome is very dynamic and changes rapidly and dramatically in response to any change or even during cellular events such as DNA replication, cell division, apoptosis or neoplastic transformation. In oncology, microarrays resulted in a better understanding of the molecular basis of many cancers, allowing the creation of a new classification of some tumor histotypes and the identification of new molecular markers useful for predicting prognosis and response to treatment. The technique has then allowed revolutionizing diagnosis, prognosis and screening of many neoplasms, and because of its high informativeness was chosen as a method of investigation for correlating molecular phenotype and response to treatment with Lapatinib.
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Abstract
The human genome sequencing has recently led to a real revolution in medicine. The post-genomic era is characterized by a new phase of biomedical research, which pays particular attention to two pharmacological disciplines known as pharmacogenetics and pharmacogenomics. Pharmacogenetics studies the individual variation in the DNA sequence (polymorphisms) in relation to drug response. One practical application of pharmacogenetics research consists in the possibility of predicting a patient's response to a certain drug on the basis of a genetic test, making it possible a tailored therapy ("the right drug at right patient"). Pharmacogenomics, studying interactions between genes, metabolic pathways and protein networks, tries to identify how both new and old drugs can interact in these networks.
It’s well known that response to xenobiotics can be very diverse in terms of failure or partial effectiveness and appearance of side effects, even making harmful to some individuals a compound otherwise harmless or benefic for others. The promise of pharmacogenetics and pharmacogenomics is to determine tolerance and responsiveness to a given drug, thus allowing the identification of the active compounds that appear to be more effective in each single patient for specific disease treatment.
For what concerns breast cancer, it encompasses a broad variety of diseases, that differ in terms of prognosis and response to therapeutic treatment. Determining such differences lead to a better diagnosis and prognosis prediction, and allows the design of a more targeted and personalized drug treatment, improving its effectiveness and reducing the risk and extent of side effects. The study of gene expression profiles of individual carcinomas at the time of clinical diagnosis was then inserted with this aim in two sets of therapeutic experimental protocols on using the drug Lapatinib (GW572016). The study was carried out using the Affymetrix GeneChip platform.
Microarray technology is one of the most powerful and flexible tools of the post-genomic era and makes it possible to collect information on thousands of genes, drawing an overall picture of gene expression. The whole of genes transcribed from genomic DNA is called "expression profile" or transcriptome and defines the molecular phenotype of a cell and therefore its functions. In contrast to genome, transcriptome is very dynamic and changes rapidly and dramatically in response to any change or even during cellular events such as DNA replication, cell division, apoptosis or neoplastic transformation. In oncology, microarrays resulted in a better understanding of the molecular basis of many cancers, allowing the creation of a new classification of some tumor histotypes and the identification of new molecular markers useful for predicting prognosis and response to treatment. The technique has then allowed revolutionizing diagnosis, prognosis and screening of many neoplasms, and because of its high informativeness was chosen as a method of investigation for correlating molecular phenotype and response to treatment with Lapatinib.
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