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Old 02-12-2012, 11:40 PM   #4
gdpawel
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Re: any tumor tests to predict which chemos work better?

The only thing I can tell you about Caris is that the only truly useful information relates to the common markers which are tested in most pathology laboratories, i.e. ER, PR, Her2, etc. Maybe DHFR (dihydrofolate reductase).

Caris begins with an immunohistochemistry (IHC) analysis. IHC testing examines "dead" tissue. An IHC test measures the level of proteins in cancer cells providing clues about which therapies are likely to have clinical benefit and then what additional tests should be run. It never actually tests your tumor specimen against any drug agents.

If deemed appropriate, they will run additional tests. Fluorescent In-Situ Hybridization (FISH) is used to examine gene copy number variation in the tumor. Polymerase Chain Reaction (PCR) or DNA sequencing is used to determine gene mutations in the DNA of the tumor.

It is a tumor analysis coupled with clinical literature search, which tries to match therapies to patient-specific biomarker information to generate a treatment approach. In other words, information that may help when considering "potential" treatment options (theoretical analysis).

Rational Therapeutics and Weisenthal Cancer Group both use a functional profiling platform. It takes the tumor with the surrounding tissue (intact and live) and then puts chemo on it to see which chemos (actually) kill the cancer cells.

The ability to monitor cell "function" provides clinicians with a vital method to characterize and compare activity of cells. Programmed cell death, or apoptosis, is critical in cancer formation and is often used to determine if cells are functioning properly.

Phenotype (functional profiling) analyses, measure biological signals rather than DNA indicators, provides clinically validated information and plays an important role in cancer drug selection. The data that support phenotype analyses is demonstrably greater and more compelling than any data currently generated from genotype analyses.

Funtional profiling "actually" measures the response of the tumor cells to drug exposure. Following this exposure, they measure both cell metabolism and cell morphology. The integrated effect of the drugs on the whole cell, resulting in a cellular response to the drug, measuring the interaction of the entire genome. No matter which genes are being affected, functional profiling is measuring them through the surrogate of measuring if the cell is alive or dead.

Caris is testing for mutations, RT and WCG are testing for drugs. Rating the efficacy of population research vs rating the efficacy of drugs actually tested against an individual's cancer cells.

The endpoints (point of termination) of molecular profiling (genotyping analysis) are gene expression, examining a single process (pathway) within the cell or a relatively small number of processes (pathways) to test for "theoretical" candidates for targeted therapy.

The endpoints of functional profiling (phenotyping analysis) are expression of cell-death, both tumor cell death and tumor associated endothelial (capillary) cell-death (tumor and vascular death), and examines not only for the presence of the molecular profile but also for their functionality, for their interaction with other genes, proteins and other processes occuring within the cell, and for their "actual" response to anti-cancer drugs (not theoretical susceptibility).

Again, the choice is theoretical vs actual analysis.

Greg
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