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Old 05-14-2009, 07:28 PM   #2
gdpawel
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What is the clinical relevance of molecular profiling?

In chemotherapy selection, molecular profiling 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.

Functional profiling tests not only for the presence of the molecular profile but also for their functionality, for their interaction with other genes, proteins, and processes occurring within the cell, and for their response to anti-cancer drugs.

The goal of molecular testing is to look for patterns of normal and abnormal gene expression which could suggest that certain proteins might or might not be produced within a cell. However, just because a gene is present, it does not mean that an associated protein has been produced.

Protein testing goes one step further by testing to see if the relevant protein actually has been produced. However, even Protein testing cannot tell us if a protein is functional or how it will interact with other proteins in the presence of anti-cancer drugs.

Gene and protein testing involve the use of dead, formaldehyde preserved cells that are never exposed to chemotherapy drugs. Gene and protein tests cannot tells us anything about uptake of a certain drug into the cell or if the drug will be excluded before it can act or what changes will take place within the cell if the drug successfully enters the cell.

Gene and protein tests cannot discriminate among the activities of different drugs within the same class. Instead, gene and protein tests assume that all drugs within a class will produce precisely the same effect, even though from clinical experience, this is not the case. Nor can gene and protein tests tell us anything about drug combinations.

Functional tumor cell profiling tests living cancer cells. It assesses the net result of all cellular processes, including interactions, occurring in real time when cancer cells actually are exposed to specific anti-cancer drugs. It can discriminate differing anti-tumor effects of different drugs within the same class. It can also identify synergies in drug combinations.

Gene and protein tests are better suited for ruling out "inactive" drugs than for identifying "active" drugs. When considering a cancer drug which is believed to act only upon cancer cells that have a specific genetic defect, it is useful to know if a patient's cancer cells do or do not have precisely that defect.

Although presence of a targeted defect does not necessarily mean that a drug will be effective, absence of the targeted defect may rule out use of the drug. Of course, this assumes that the mechanism of drug activity is known beyond any doubt, which is not always the case.

Although gene and protein testing currently are limited in their reliability as clinical tools, the tests can be important in research settings such as in helping to identify rational targets for development of new anti-cancer drugs.

As you can see, just selecting the right test to perform in the right situation is a very important step on the road to personalizing cancer therapy.

Source: Cell Function Analysis
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