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Old 02-07-2013, 04:06 PM   #5
gdpawel
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Which Personalized Chemotherapy Testing Methods Are More Direct? Part I

Whole Organism Testing

The most direct way to see if a chemotherapy drug will work is to administer it to the patient and see what happens. This is how most drugs are administered. Each patient, in effect, becomes his/her own experiment. If the drug(s) does not work, the patient needlessly suffers harmful side-effects, valuable treatment time is wasted, costs are incurred and the surviving tumor cells may become more resistant to all chemotherapy drugs, including drugs which the patient has not received. This is what is called clinically-acquired multi-drug resistance. Since patients cannot endure exposure to all of the available chemotherapy drugs, many potentially effective drugs will go untested. Also, since chemotherapy drugs commonly are administered in combination, there is no way to know which drug or drugs in a particular combination may have been more effective and which were less effective or not effective at all.

Cytometric Cancer Testing (Functional Profiling)

It pinpoints the ability of each drug to kill each patient's actual cancer cells. It 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.

Protein Testing

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 is more direct than RNA testing because it reveals whether or not a protein which theorectially 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.

Messenger RNA Testing

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. 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.

DNA Testing (Molecular Profiling)

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 even occurring at the other end of a highly complex process. Even if all genetic factors were understood, which they are not, 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.

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