Functional Profiling versus Static Profiling
(Gene Testing versus Protein Testing versus Whole Cell Testing)
Many researchers are working to develop gene and protein-based tests to aid
in therapy selection. A small
number of these tests are already in use but so far they are confined to
very specific clinical settings.
Gene and protein-based tests are much easier to perform than the
whole cell Functional Tumor Cell Profiling tests used by Weisenthal Cancer
Group but the information they provide is correspondingly far more limited.
Here is a quick explanation:
Gene and protein testing are indirect approaches to chemotherapy selection
which examine a single process within the cell or a relatively small number
of processes. Their aim is to
tell us only if there is a theoretical predisposition to drug response.
In this regard, gene and protein testing may be thought of as
“Partial Cell Static Profiling.”
This differs from the “Whole Cell Functional Profiling” method we use
at Weisenthal Cancer Group, in which we test not for only for the presence
of genes and proteins but also for their functionality, for their
interaction with other genes, proteins, and processes occurring within the
cell, and for their response to anti-cancer drugs.
Genes create the blueprints for the production of proteins within the cell.
The term “Protein” is not used here in a nutritional sense.
A protein is a molecule that makes a cell behave in a certain way.
It does so by interacting with other proteins in a complex series of
steps.
The goal of gene testing is to look for patterns of normal and abnormal gene
expression which could suggest that certain proteins might or might not be
produced within a cell. However,
just because a gene is present it does not mean that an associated protein
has been produced. Protein
testing goes one step further by testing to see if the relevant protein
actually has been produced.
However, even protein testing cannot tell us if a protein is functional or how it
will interact with other proteins in the presence of anti-cancer drugs.
Gene and protein testing involve the use of dead, formaldehyde preserved
cells that are never exposed to
chemotherapy drugs. Gene and
protein tests cannot, therefore, tells us anything about uptake of a certain
drug into the cell or if the drug will be excluded before it can act or what
changes will take place within the cell if the drug successfully enters the
cell. Gene and protein tests
also cannot discriminate among the activities of different drugs within the
same class. Instead gene and
protein tests assume that all drugs within a class will produce precisely
the same effect, even though we know from clinical experience that this is
not the case. Nor can gene and
protein tests tell us anything about drug combinations.
In contrast, functional tumor cell profiling tests living cancer cells.
Functional Tumor Cell Profiling assesses the net result of all
cellular processes, including interactions, occurring in real time when cancer cells actually are
exposed to specific anti-cancer drugs.
Functional profiling can therefore discriminate differing anti-tumor
effects of different drugs within the same class.
Functional Profiling can also identify synergies in drug
combinations.
This is not intended as a criticism of gene and protein-based testing.
Rather, it is intended only to point out the fact that, in their
current state of development, gene and protein tests are better suited for
ruling out inactive drugs than for identifying active drugs.
For example, when considering a cancer drug which is believed to act
only upon cancer cells that have a specific genetic defect, it is useful to
know if a patient's cancer cells do or do not have precisely that defect.
Although presence of a targeted defect does not necessarily mean that
a drug will be effective, absence of the targeted defect may rule out use of
the drug.
Of course, this assumes that the mechanism of drug activity is known beyond
any doubt, which is not always the case.
Although gene and protein testing currently are limited in their
reliability as clinical tools, the tests can be important in research
settings such as in helping to identify rational targets for development of
new anti-cancer drugs.
As you can see, just selecting the right test to perform in the right
situation is a very important step on the road to personalizing therapy.