The EGFRx (TM) assay will test
molecularly-targeted anti-cancer drugs therapies Iressa, Tarceva, Sutent
and possibly Nexavar, because of being small molecules. The monoclonal
antibodies like Herceptin and Erbitux are "enormous" molecules. These
very large molecules don't have a convenient way of getting access to
the large majority of cells. Plus, there is multi-cellular resistance,
the drugs affecting only the cells on the outside may not kill these
cells if they are in contact with cells on the inside, which are
protected from the drug. The cells may pass small molecules back and
forth.
However, drugs like Avastin
(although a monoclonal antibody) can be tested with EGFRx (TM) because
the target of Avastin is not the cells themselves, but rather a hormone
(VEGF) secreted by the tumor cells. The Avastin complexes with free VEGF
and blocks its action. The EGFRx (TM) test can discriminate between the
activities of different targeted drugs and identify situations in which
it is advantageous to combine the targeted drugs with other types of
cancer drugs. All the more reason to "test the tumor first."
Most patients are treated not with a
targeted therapy drug alone but with a combination of chemotherapy
drugs. Therefore, existing DNA and RNA tests do not reflect the way
cancer medicine is practiced today. The EGFRx assay, developed by The
Weisenthal Cancer Group relies upon a technique known as “Whole Cell
Profiling” in which living tumor cells are removed from an individual
cancer patient and exposed in the laboratory to the new drugs.
A variety of metabolic and apoptotic
measurements are then used to determine if a specific drug was
successful at killing the patient's cancer cells. The whole cell
profiling method differs from other tests in that it assesses the
activity of a drug upon combined effect of all cellular processes, using
several metabolic and morphologic endpoints. Other tests, such as those
which identify DNA or RNA sequences or expression of individual proteins
often examine only one component of a much larger, interactive process.
“Over the past few years,
researchers have put enormous efforts into genetic profiling as a way of
predicting patient response to targeted therapies. However, no
gene-based test as been described that can discriminate differing levels
of anti-tumor activity occurring among different targeted therapy
drugs,” said Larry Weisenthal, a medical oncologist and developer of the
EGFRxTM assay. “Nor can an available gene-based test identify
situations in which it is advantageous to combine a targeted drug with
other types of cancer drugs. So far, only whole profiling has
demonstrated this critical ability.”
Not only is this an important
predictive test that is available "today," but it is also a unique tool
that can help to identify newer and better drugs, evaluate promising
drug combinations, and serve as a "gold standard" correlative model with
which to develop new DNA, RNA, and protein-based tests that better
predict for drug activity.
These "targeting" drugs are
expensive, costing patients and insurance carriers $5,000 to $7,000 or
more per month of treatment. Patients, physicians, insurance carriers,
and the FDA are all calling for the discovery of predictive tests that
allow for rational and cost-effective use of these drugs.
Weisenthal believes that the cell profiling approach holds the key to
solving some of the problems confronting a healthcare system that is
seeking ways to best allocate available resources while accomplishing
the critical task of matching individual patients with the treatments
most likely to benefit them.
By Gregory D. Pawelski
Freelance Writer
About the writer: Gregory D. Pawelski
writes, I was a spouse/caregiver to an ovarian
cancer patient. I became intensely interested in cancer medicine by
virtue of working through, enduring and surviving my wife's illness.
I've gotten a street education by virtue of voluminous reading and
hundreds of hours of past and ongoing personal communication with noted
authorities in the field. To paraphrase Martin Luther King Jr: "A
scientific communication should be judged on the quality of its content
and only secondarily, or not at all, on the qualifications of its
author."
Books on Cancer
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