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Pancreas Cancer

Chemosensitivity Testing was posted 08/31/2012 07:52 pm by gpawelski
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Anonymous

'Chemosensitivity testing' is sometimes misunderstood. I just want to explain the differences in assay methodologies. The phrase 'chemosensitivity assay' has been used out of context by a lot of people. There is molecular profiling (genomic/proteomic analysis) and there is functional profiling (cell function analysis). The former testing (genotype) is theoretical and the latter (phenotype) is actual.

In drug selection, molecular (genetic) testing examines a single process within the cell or a relatively small number of processes. The aim is to tell if there is a theoretical predisposition to drug response. It attempts to link surrogate gene expression to a theoretical potential for drug activity. Patients' cancer cells are never exposed to chemotherapy drugs. It relies upon a handful of gene patterns which are thought to imply a potential for drug susceptibility. In other words, molecular testing tells us whether or not the cancer cells are potentially susceptible to a mechanism or pathway of attack. It doesn't tell you if one drug is better or worse than another drug which may target a certain mechanism or pathway.

Functional profiling doesn't dismiss DNA testing, it uses all the information, both genomic and functional, to design the best treatment for each individual, not populations. Laboratories like Rational Therapeutics and Weisenthal Cancer Group test for a lot more than just a few mutations. The cell is a system, an integrated, interacting network of genes, proteins and other cellular constituents that produce functions. One needs to analyze the systems' response to drug treatments, not just a few targets (mechanisms or pathways).

The functional profiling test (a 'real' chemosensitivity test) assesses the activity of a drug upon combined effect of all cellular processes, using several metabolic (cell metabolism) and morphologic (structure) endpoints, at the cell 'population' level, rather than at the 'single cell' level, measuring the interaction of the entire genome.

Examining a patient's DNA can give physicians a lot of information, but as the NCI has concluded (J Natl Cancer Inst. March 16, 2010), it cannot determine treatment plans for patients. It cannot test (chemo) sensitivity to any of the targeted therapies, just 'theoretical' candidates for targeted therapy.

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