Functional Profiling versus Static Profiling
(Gene Testing versus Protein Testing versus Whole Cell Testing)
Numerous 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 easier to perform than the whole
cell Functional Tumor Cell Profiling tests used by Weisenthal Cancer Group
but the information they provide is correspondingly more limited.
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
determine 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 in 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.
Gene-based tests identify patterns of normal and abnormal gene expression
that suggest that certain proteins might be produced within a cell.
However, gene expression is not protein production.
Protein testing goes one step further by testing to see if the relevant
protein actually has been produced.
However, 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 non-viable, formalin-fixed 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 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.
While 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.