1. genetic testing is exciting, but very new. In one study of lung cancer treatment:

"Overall time to progression was 5.33 months (95% CI 4.2–5.6). Time to progression according to ERCC1 SNP genotype was 4.1 months (95% CI 1.2–6.9) for 34 patients heterozygous for C/T and 5.8 months (95% CI 3.8–7.8) for 17 patients homozygous for the rare alleles T/T, while it was 8.4 months (95% CI 3.2–13.6) for 11 patients homozygous for the wild-type C/C (P=0.03). Time to progression was 5.3 months (95% CI 4–6.6) for all 51 patients with non-wild-type genotypes considered as one group (P=0.02). No other significant differences in time to progression were observed according to SNP genotype."

There was a difference but it wasn't great. As far as testing different chemotherapy regimens? Well, we have little evidence of that at all despite what one may hear from bloggers and a few scientists. Luckily, those prospective studies are now beginning.

http://annonc.oxfordjournals.org/cgi/content/full/15/8/1194#F1

Posted at 8:36PM on Sep 12th 2006 by Michelle

2. Improving cancer patient diagnosis and treatment through a combination of cellular and gene-based testing will offer predictive insight into the nature of an individual's particular cancer and enable oncologists to prescribe treatment more in keeping with the heterogeneity of the disease. The biologies are very different and the response to given drugs is very different.

Over the past few years, gene expression profiling has been suggested as the best or only way of determining ex vivo drug sensitivity. However, the clinical application of these DNA content assays have been shown to correlate only with response and not survival. And due to almost all patients being treated with combination chemotherapy, this methodology cannot even be calibrated without the use of whole cell profiling. Cell function analysis with whole cell profiling can actually integrate all the gene expression into one convenient test result.

In obtaining information from gene mutations (DNA content assays) and/or gene expression (RNA content) it must be realized that DNA structure is only important insofar as it predicts for RNA content, which is only important insofar as it predicts for protein content, which is only important insofar as it predicts for protein function, which is only important insofar as it predicts for cell response, which is only important insofar as it predicts for tumor response and function. In other words, it correlates only with response and not survival, in entirely retrospective (not prospective) studies.

There is whole cellular profiling (Cell Function Analysis) that shows data indicating a near doubling in the survival of patients with platinum resistant ovarian cancer, striking correlations between platinum activity and patient survival in previously-untreated ovarian cancer, and a comprehensive meta-analysis of scores of studies reporting response and survival correlations in thousands of patients.

Plus a recent study using angiogenesis assay describing correlations between cell culture assay results in response to Iressa, and survival in patients with non-small cell lung cancer. These correlations were based on the actual assay results which had been reported, in real time, prospectively to the doctors who had ordered the assay laboratory tests. There were striking correlations between test results and patient survival, not just response.

Not only is whole cellular profiling a very important predictive test, but it is a unique tool for identifying newer, better drugs, testing drug combinations, and serving as a "gold standard" to develop new DNA, RNA, and protein-based tests of drug activity.

Posted at 1:03AM on Sep 24th 2006 by Gregory D. Pawelski