HER2 Support Group Forums - View Single Post - insufficient her2 testing--not enough patients given possibility of benefiting from

gdpawel · 09-15-2009, 05:43 AM

To get the new genetic/molecular tests, the validation standard that all the private health insurance companies is accepting is accuracy. The essential proof is that all they have to do for these tests is that the test has a useful degree of accuracy. The traditional criteria ever used to evaluate laboratory tests has always been the predictive accuracy of the test.

However, the headlong rush to develop companion diagnostics to identify molecular predisposing mechanisms still does not guarantee that a cancer drug will be effective for individual cancer patients. Nor can they discriminate the potential for clinical activity among different cancer agents of the same class.

The drug discovery model has been limited to one gene/protein, one target, one drug. The "cell" is a system, an integrated, interacting network of genes, proteins and other cellular constituents that produce functions. You need to analyse the systems' response to drug treatments, not just one target or pathway.

Uncovering the genetic differences that determine how a person responds to a drug, and developing tests, or biomarkers, for those differences, is proving more challenging than ever. As a result, patients with cancer are still being prescribed medicines on a trial-and-error basis.

The key to understanding the genome is understanding how cells work. The ultimate driver is "functional" diagnostics (is the cell being killed regardless of the mechanism) as opposed to "target" diagnostics (does the cell express a particular target that the drug is supposed to be attacking).

While a "target" diagnostic test tells you whether or not to give "one" drug, a "functional" diagnostic test can find other compounds and combinations and can recommend them from the one test.

The core of functional diagnostics is the cell, composed of hundreds of complex molecules that regulate the pathways necessary for vital cellular functions. If a targeted drug could perturb any one of these pathways, it is important to examine the effects of the drug within the context of the cell. Both genomics and proteomics can identify potential new thereapeutic targets, but these targets require the determination of cellular endpoints.

The cell "function" methodology measures the net effect of all processes within the cancer, acting with and against each other in real-time, and it tests "living" cells "actually exposed" to drugs and drug combinations of interest.

Many hope that molecular tests may hold the key to success, particularly as more specific drugs are designed to hit the molecular changes that are responsible for the uncontrolled growth of cancer cells. However, most drugs cannot be looked at in this way and tests that are now in use have limited predictive accuracy. There is no single gene whose expression accurately predicts therapy outcome.

09-15-2009, 05:43 AM	#7
gdpawel Senior Member Join Date: Aug 2006 Location: Pennsylvania Posts: 1,080	Companion Diagnostics To get the new genetic/molecular tests, the validation standard that all the private health insurance companies is accepting is accuracy. The essential proof is that all they have to do for these tests is that the test has a useful degree of accuracy. The traditional criteria ever used to evaluate laboratory tests has always been the predictive accuracy of the test. However, the headlong rush to develop companion diagnostics to identify molecular predisposing mechanisms still does not guarantee that a cancer drug will be effective for individual cancer patients. Nor can they discriminate the potential for clinical activity among different cancer agents of the same class. The drug discovery model has been limited to one gene/protein, one target, one drug. The "cell" is a system, an integrated, interacting network of genes, proteins and other cellular constituents that produce functions. You need to analyse the systems' response to drug treatments, not just one target or pathway. Uncovering the genetic differences that determine how a person responds to a drug, and developing tests, or biomarkers, for those differences, is proving more challenging than ever. As a result, patients with cancer are still being prescribed medicines on a trial-and-error basis. The key to understanding the genome is understanding how cells work. The ultimate driver is "functional" diagnostics (is the cell being killed regardless of the mechanism) as opposed to "target" diagnostics (does the cell express a particular target that the drug is supposed to be attacking). While a "target" diagnostic test tells you whether or not to give "one" drug, a "functional" diagnostic test can find other compounds and combinations and can recommend them from the one test. The core of functional diagnostics is the cell, composed of hundreds of complex molecules that regulate the pathways necessary for vital cellular functions. If a targeted drug could perturb any one of these pathways, it is important to examine the effects of the drug within the context of the cell. Both genomics and proteomics can identify potential new thereapeutic targets, but these targets require the determination of cellular endpoints. The cell "function" methodology measures the net effect of all processes within the cancer, acting with and against each other in real-time, and it tests "living" cells "actually exposed" to drugs and drug combinations of interest. Many hope that molecular tests may hold the key to success, particularly as more specific drugs are designed to hit the molecular changes that are responsible for the uncontrolled growth of cancer cells. However, most drugs cannot be looked at in this way and tests that are now in use have limited predictive accuracy. There is no single gene whose expression accurately predicts therapy outcome.