[gdpawel]

The problem is in gene sequencing. Sequencing the genome of cancer cells is explicitly based upon the assumption that the pathways - network of genes - of tumor cells can be known in sufficient detail to control cancer. Each cancer cell can be different and the cancer cells that are present change and evolve with time. Cancer cells often have many mutations in many different pathways, so even if one route is shut down by targeted treatment, the cancer cell maly be able to use other routes.

In other words, cancer cells have "backup systems" that allow them to survive. The result is that the drug does not shrink the tumor as expected. The cancer state is typically characterized by a signaling process that is unregulated and in a continuous state of activation.

A challenge facing pharmacogenetics is the number and complexity of interactions a drug has with biological molecules in the body. Variations in many different molecules may influence how someone responds to a medicine. There is a great degree of variation in how people absorb drugs. Individuals have different levels of enzymes in the intestines and liver that breaks down drugs before they even have the chance to get into the bloodstream. Teasing out the genetic patterns associated with particular drug responses could involve some intricate and time-consuming scientific detective work.

These new targeted drugs mostly need to be combined with active chemotherapy to provide any benefit and the need for predictive tests for individualized therapy selection has increased. Given the technical and conceptual advantages of the functional profiling platform, together with its performance and the modest efficacy of therapy prediction based on analysis of genome expression, there is reason for a renewal in there interest for optimized use of medical treatment of malignant disease.

The NCI has concluded, gene-guided chemotherapy (gene signatures) cannot determine treatment plans for patients. It cannot test sensitivity to any of the targeted therapies. It just tests for theoretical candidates for targeted therapy. And due to almost all patients being treated with combination chemotherapy, the molecular profiling methodology cannot even be calibrated without the use of cell-based functional profiling analysis. Cell-based functional profiling can actually integrate all the gene expresslion into one convenient test result.