[gdpawel]

I remember two years ago, researchers at The Institute of Cancer Research in London, using "cell-lines" to functionally profile using high-throughput screening with chemical and siRNA libraries in clear cell ovarian cancer (J Clin Oncol 30, 2012, suppl; abstr 5035). It was only a "cell-line" study, but it was gratifying to see that someone picked up on the "functional profiling" moniker.

Microarrays (gene chips) examine what genes are expressed in cancer cells. It is mainly used for screening/gene discovery work. You screen 50,000 genes to discover an association and then you focus in on only a few hundred or so for more careful study by some other method like real time polymerase chain reaction (RT-PCR).

Genes make proteins, the molecules that comprise and maintain all the body's tissues. Genes produce their effect by sending molecules called messenger RNA to the protein-making machinery of a cell. They set the protein-making machinery in motion through a "gofer" messenger called RNA (or mRNA).

The technique called RNA interference (RNA-i) allows scientists to "silence" certain genes. In RNA interference, certain molecules trigger the destruction of RNA from a particular gene, so that no protein is produced. Thus, the gene is effectively silenced. RNA interference is already being widely used in basic science as a method to study the function of genes and it is being studied as a treatment for cancer.

This RNA interference occurs naturally in plants, animals, and humans. RNA interference is important for regulating the activity of genes (a fundamental mechanism for controlling the flow of genetic information). RNA interference (RNAi) interferes with mRNA, a natural molecular switch, regulating gene expression in plants, animals and humans, by "silencing" over-active or malfunctioning genes.

The ability to introduce foreign DNA into cultured cells with DNA gene sequences has allowed us to assign functions to different genes and understand the mechanisms that activate or redress their function. It has made gene therapy research possible, like with the proteins Dicer and Drosha.

However, giving instructions on the genetic differences that determine how a person responds to a drug will still have cancer medicine being prescribed on a "trial-and-error" basis, with adverse drug reactions remaining a major cause of injury and hospitalizations.

All the gene mutation or amplification studies can tell us is whether or not the cells are potentially susceptible to this mechanism of attack. The don't tell you if one drug is better or worse than some other drug which may target this.

The cell is a system, an intergrated, interacting network of genes, proteins and other cellular constituents that produce functions. You need to analyze the systems' response to drug treatments, before you find clinical responders.

Genetic profiles cannot discriminate differing levels of anti-tumor activity occurring among different targeted therapy drugs. Nor can they identify situations in which it advantageous to combine a targeted drug with other types of conventional cancer drugs.

Three federal agencies, NCI, FDA, and CMS, announced a program to try to identify biological indicators, or biomarkers, which may indicate whether a cancer patient is likely to benefit from a given anti-cancer therapy, or even whether they will suffer from certain side effects.

We have the biomarkers for who will respond so we don't give these powerful and expensive medicines to those who won't. Technologies, developed over the last twenty years by private researchers, hold the key to solving some of the problems confronting a healthcare system that is seeking ways to best allocate available resources while accomplishing the critical task of matching individual patients with the treatments most likely to benefit them.