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Cancer Treatments - New Tests Helps to Determine the Effectiveness of Targeted Cancer Drugs

June 26th, 2006

Cancer Treatments - New Tests Helps to Determine the Effectiveness of Targeted Cancer Drugs

Close ups of Cells
image courtesy of Sandia

A new laboratory test that identifies patients who benefit most from targeted cancer drugs was introduced at the annual meeting of the American Society of Clinical Oncology (ASCO) as the test's accuracy is sure to save hundreds of lives per year. This could help solve the problem of knowing which patients can tolerate costly, new treatments and their harmful side-effects. These “smart” drugs do not work for everyone, and a test to determine the efficacy of these drugs in a patient could be the first crucial step in personalizing treatment to the individual.


According to Chemical & Engineering News, targeted "small-molecule" therapies ruled at the annual ASCO meeting of oncologists. The most exciting results shown came from studies of multi-targeted tyrosine kinase inhibitors, small molecules that act on multiple receptors in the cancerous cells, like Tykerb and Sutent. The trend is away from the monoclonals to the small molecules, a trend which the new EGFRx (TM) test may be able to hasten.

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.

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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."

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Copyright 2005 Best Syndication                   Last Updated Saturday, July 10, 2010 09:46 PM