[gdpawel]

Is the microchip arrays just an alternative to RT-PCR or is it inferior to RT-PCR?

Basically, RT-PCR is more accurate, but it can't be done on such a massive scale. RT-PCR is practical for testing tens to hundreds of genes, while microchip arrays can be used for thousands to tens of thousands of genes.

The use of RT-PCR and DNA microchip arrays in personalized oncology is analogous to the introduction of the personal computer. Dazzling hardware in search of a killer application. This was wonderful technology and the geekiest of people bought them and played with them, but they really didn't start to do anything for a mass market until the introduction of the first killer application, which was a spreadsheet program called Visicalc.

So what research scientists in universities and cancer centers have been doing for the past ten years is to try and figure out a way to use this dazzling technology to look for patterns of gene expression which correlate with and predict for the activity of anticancer drugs. Hundreds of millions of dollars have been spent on this effort.

Academics are besides themselves over the promise of genome sequencing. It seems so cool that it simply must be good for something. How about in the area of identifying drugs which will work in individual patients? All DNA or RNA-type tests are based on "population" research. They base their predictions on the fact that a higher percentage of people with similar genetic profiles or specific mutations may tend to respond better to certain drugs. This is not really "personalized" medicine, but a refinement of statistical data.

The particular sequence of DNA that an organism possess (genotype) does not determine what bodily or behaviorial form (phenotype) the organism will finally display. Among other things, environmental influences can cause the suppression of some gene functions and the activation of others. Our knowledge of genomic complexity tells us that genes and parts of genes interact with other genes, as do their protein products, and the whole system is constantly being affected by internal and external environmental factors.

The gene may not be central to the phenotype at all, or at least it shares the spotlight with other influences. Environmental tissue and cytoplasmic factors clearly dominate the phenotypic expression processes, which may in turn, be affected by a variety of unpredictable protein-interaction events. This view is not shared by all molecular biologists, who disagree about the precise roles of genes and other factors, but it signals many scientists discomfort with a strictly deterministic view of the role of genes in an organism's functioning.

It could be vastly more beneficial to measure the net effect of all processes (systems) instead of just individual molecular targets. 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 drug treatments, not just one or a few targets (pathways/mechanisms).

There are many pathways/mechanisms to the altered cellular (forest) function, hence all the different "trees" which correlate in different situations. Improvement can be made by measuring what happens at the end (the effects on the forest), rather than the status of the indivudal trees.

The "success" or "failure" is in the drug or drug combinations. Cell function analysis doesn't change cancer biology, it helps to "reveal" the cancer biology. It lowers the "probability" that certain drugs won't work, and raises the "probability" that others will work. The functional profiling platform is showing the "effaciousness" of the particular drug or drug combinations.