Tissue culture: unlocking the mysteries of viruses and cancerBMJ 2007; 334 doi: https://doi.org/10.1136/bmj.39034.719942.94 (Published 04 January 2007) Cite this as: BMJ 2007;334:s18
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The study of Cell Function Analysis tells us that even when the
disease is the same type, different patients' tumors respond differently
to the same agents. So it doesn't matter if there is a "target" molecule
in the cell that the "targeted" drug is going after, if the drug either
won't "get in" in the first place or if it gets pumped out/extruded or if
it gets immediately metabolized inside the cell, drug resistance is
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 applicaton 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 Cell Function Analysis. This
analysis 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
important only 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.
What are the data supporting the use of testing DNA, RNA and Protein
expression? Two retrospective studies from two Harvard-affiliated
hospitals, showing response, but not survival advantages, with a grand
total of twenty six correlations. And a subsequent study, presented in the
July 14, 2005 issue of the New England Journal of Medicine from another
laboratory that did not show correlations between gene mutations and
patient survival (Volume 353:133-144 Number 2).
There is Cell Function Analysis (functional profiling) 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 an angiogenesis assay describing
correlations between cell culture assay results 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
Not only is 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.
Source: Various Bio-Assay Labs
Competing interests: No competing interests