Researchers have seen that whether a tumor was a breast tumor, prostate tumor, lung tumor or colon tumor, it didn't correlate to how the cancers interacted with standard anticancer drugs. Their findings suggest that traditional cancer treatments, which have established different drug regimens for lung, prostate or ovarian cancer, for example, should be replaced with therapies that use drugs deemed to be of highest benefit based on the tumor's pharmacologic profile. Treatment choice would be determined by how each patient's tumor reacts to anticancer drugs, regardless of the tumor's anatomical origin.
The drug effect is independent of where the tumor came from in the body. Under current treatment selection methods virtually no chemotherapeutic drug has been successful in more than 50 percent of patients with advanced cancer. But instead of considering a drug that works only ten percent of the time a failure, it would be better to consider such a drug effective for one in ten tumors and to search for the agents among the current arsenal of chemotherapeutic drugs that will work for the rest. Having a good tumor-drug match not only would improve survival rates, it would be cost-effective, and the high cost of the newer cancer therapies reinforces the necessity of choosing the right therapy the first time around.
The introduction of new "targeted" drugs has not been accompanied by specific predictive tests allowing for a rational and economical use of the drugs. Given the technical and conceptual advantages of Cell Culture Assays together with their performance and the modest efficicay of therapy prediction on analysis of genome expression, there is reason for a renewal in the interest for these for optimized use of medical treatment of malignant disease.
Clinical study results published at the annual meeting of the American Society of Clinical Oncology (ASCO) show that a new laboratory test, called EGFRx™, has accurately identified patients who would benefit from treatment with the molecularly-targeted anti-cancer therapies. The finding is important because the EGFRx™ test, which can also be applied to many emerging targeted cancer drugs, could help solve the growing problem of knowing which patients should receive costly, new treatments that can have harmful side-effects and which work for some but not all cancer patients who receive them. The test can discriminate between the activity of different targeted drugs and identify situations in which it is advantageous to combine the targeted drugs with other types of cancer drugs.
The new test relies upon what is called "Functional 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 combined 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.
The whole cell profiling method makes the statistically significant association between prospectively reported test results and patient survival. Using the EGFRx™ Assay and the "functional profiling" method, can correlate test results which are obtained in the lab and reported to physicians prior to patient treatment, with significantly longer or shorter overall patient survival depending upon whether the drug was found to be effective or ineffective at killing the patient's tumor cells in the laboratory.
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 has been described that can discriminate differing levels of anti-tumor activity occurring among different targeted therapy drugs. 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 cell 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.
The whole 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.
Genomic testing is not the answer, without cell culture analysis. In developing a program to discover gene expression microarrays, which predict for responsiveness to drug therapy, the way to identify informative gene expression patterns is to have a gold standard and that cell culture assays are by far the most powerful, efficient, useful gold standard to have.
The assay is the only assay that involves direct visualization of the cancer cells at endpoint. This allows for accurate assessment of drug activity, discriminates tumor from non-tumor cells, and provides a permanent archival record, which improves quality, serves as control, and assesses dose response in vitro (includes newly-emergent drug combinations).
Oct 23, '06
Research has shown that controlling production of new blood vessels can restrict tumor growth, often prolonging the life of the cancer patient. Perhaps the most widely-used anti-angiogenic agent to emerge to date is a drug called Avastin. Avastin was approved by the FDA for use in combination with intravenous 5-fluorouracil-based chemotherapy for first-line treatment of patients with metastatic colorectal cancer. However, Avastin has also shown activity in many other solid tumor types such as breast, lung, and ovarian cancers. As with most targeted-therapy drugs, Avastin does not necessarily benefit every patient and it is expensive. Further, no test currently exists that shows reliably who will benefit from it.
The Weisenthal Cancer Group has developed an assay for microvasacular viability (M.V.V.) to identify potential responders to Avastin, Nexavar, Sutent, and other anti-angiogenic drugs and to assess previously unanticipated direct and potentiating anti-angiogenic effects of targeted therapy drugs such as Tarceva and Iressa. Prior to development of the M.V.V. assay it was thought that the lack of an intact tumor micro-vasculature would prevent in vitro drug studies in disaggregated tissues. However, it was discovered that endothelial cells are present in tumor microclusters and it appears that drug effect upon these cells can be assessed in the M.V.V. assay.
The M.V.V. assay is being offered currently to selected Weisenthal Cancer Group clients on a research basis and as an adjunct to either a Weisenthal Cancer Group standard CytoRxTM assay or an EGFRx™ tyrosine kinase assay.
Last edit by gdpawel on Nov 12, '07
: Reason: update