[gdpawel]

Located in the cell nucleus, DNA contains genetic information which causes cells to behave as they do. DNA encodes for RNA, which encodes for production of proteins. DNA is the farthest upstream factor predisposing a theoretical event occurring at the other end of a highly complex process. This is the least direct testing method (DNA testing or molecular profiling).

Even if all genetic factors were understood, the mere presence of a DNA sequence does not mean that the downstream even will occur. If a specific drug targets only a specific DNA sequence, the absence of that sequence might preclude the use of that drug.

However, even if the sequence is present, it is still impossible to know if the drug will work. No DNA test can pinpoint specific drugs in the same class or detect synergy in drug combinastions. DNA tests involve tiny fragments of cells. In DNA tests, patients' tumor cells are never exposed to any anti-cancer drugs.

RNA acts as a messenger, splitting off from the DNA helix in the cell nucleus and carrying the blueprint for production of proteinis out of the nucleus and into the cytoplasm, essentially the 'factory floor' where proteins are manufactured.

Proteins ultimately govern the behaviors of both normal cells and tumor cells. Tests which can detect the presence of specific types of RNA are a more direct method than testing the DNA because it shows that certain genetic information stored in the DNA actually is producing messenger RNA. This is a more direct testing method (RNA testing).

However, the presence of RNA only implies but does not prove that proteins were produced. The importance of all proteins is not fully understood and so the tests look for only certain RNA sequences. Also, not fully understood is how the various proteins interact to support or interfere with drug sensitivity and resistance.

Proteins are chemicals which govern cell behaviors, such as susceptibility or resistance to specific chemotherapy drugs. They are manufactured within the cell's cytoplasm from blueprints which are carried from the nucleus in the form of messenger RNA.

Protein testing (proteomic profiling) is more direct than RNA testing because it reveals whether or not a protein which theoretically was encoded for by DNA actually was produced.

However, not all proteins which are involved in response to treatment have been identified, only a small number of known proteins are tested and without additional types of testing, there is no way to tell if a protein which is present actually is functional or how it interacts with other proteins of known and unknown function.

Then there is the most direct testing method of whole cell testing (short of administering a drug to the patient and see what happens). The ability to pinpoint each drug to kill each patient's actual cancer cells (functional profiling). To accurately assesses the combined effect of the fullest possible range of genetic, chemical and mechanical interactions which govern tumor cell susceptibility to drug treatment.

Factors include the presence and functionality of proteins and how those proteins interact with all other proteins and with other intracellular and intercellular processes. It accounts for cellular drug uptake, exclusion, expulsion, DNA repair and other resistance mechanisms.

Source: Larry Weisenthal, M.D., PhD., Medical and Laboratory Director, Weisenthal Cancer Group, Huntington Beach, California