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Old 06-08-2012, 09:46 AM   #5
gdpawel
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Metabolic Profiles Are Essential For Personalizing Cancer Therapy

The genomic profile is so complicated, with one thing affecting another, that it isn't sufficient and not currently useful in selecting drugs. Because metabolic changes are complex and hard to predict, metabolic profiling will be essential for selecting best treatment.

In drug selection, molecular (genomic) testing examines a single process within the cell or a relatively small number of processes. The aim is to tell if there is a theoretical predisposition to drug response. It attempts to link surrogate gene expression to a theoretical potential for drug activity.

It relies upon a handful of gene patterns which are thought to imply a potential for drug susceptibility. In other words, molecular testing tells us whether or not the cancer cells are potentially susceptible to a mechanism/pathway of attack.

It doesn't tell you if one targeted drug (or combination of targeted drugs) is better or worse than another targeted drug (or combination) which may target a certain or a small number of mechanisms/pathways.

Functional profile testing doesn't dismiss DNA testing, it uses all the information, both genomic and functional, to design the best targeted treatment for each individual, not populations. It tests for a lot more than just a few mutations.

Functional profiling consists of a combination of a (cell morphology) morphologic endpoint and one or more (cell metabolism) metabolic endpoints. It studies cells in small clusters or micro-spheroids (micro-clusters). The combination of measuring morphologic and metabolic effects at the whole cell level.

The cell is a system, an integrated, interacting network of genes, proteins and other cellular constituents that produce functions. One needs to analyze the systems' response to targeted drug treatments, not just a few targets (pathways).

Metabolomics is a newly emerging field of "omics" research concerned with the comprehensive characterization of the small molecule metabolites in biological systems. It can provide an overview of the metabolic status and global biochemical events associated with a cellular or biological system.

An increasing focus in metabolomics research is now evident in academia, industry and government, with more than 500 papers a year being published on this subject. Indeed, metabolomics is now part of the vision of the NIH road map initiative (E. Zerhouni (2003) Science 302, 63-64&72).

Many other government bodies are also supporting metabolomics activities internationally. Studying the metabolome (along with other "omes") will highlight changes in networks and pathways and provide insights into physiological and pathological states.

The concept of Systems Biology and the prospect of integrating transcriptomics, proteomics, and metabolomics data is exciting and the integration of these fields continues to evolve at a rapid pace. Developments in informatics, flux analysis and biochemical modeling are adding new dimensions to the field of metabolomics.

To be able to walk from genetic or environmental perturbations to a phenotype to a specific biochemical event is exciting. Metabolomics has the promise to enable detection of disease states and their progression, monitor response to therapy, stratify patients based on biochemical profiles, and highlight targets for drug design.

The metabolomics field builds on a wealth of biochemical information that was established over many years.

Source:
Cell Function Analysis
The Metabolomics Society
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