CancerCompass message board discussion started by Gdpawel on 9/20/2006 http://www.cancercompass.com/message-board/message/all,6955,0.htm Tue, 02 Dec 2008 00:00:00 GMT Tue, 02 Dec 2008 00:00:00 GMT http://backend.userland.com/rss RSS.NET: http://www.rssdotnet.com/ 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 Drug Resistance Tests (CCDRTs) 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 CCDRTs 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 (TM), has accurately identified patients who would benefit from treatment with the molecularly-targeted anti-cancer therapies. The finding is important because the EGFRx (TM) 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 "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 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 (TM) assay and the whole cell 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). Gdpawel Wed, 20 Sep 2006 00:00:00 GMT Cells are the most basic structure of the body. Cells make up tissues, and tissues make up organs, such as the lungs or liver. Each cell is surrounded by a membrane, a thin layer that separates the outside of the cell from the inside. For a cell to perform necessary functions for the body and respond to its surroundings, it needs to communicate with other cells in the body. Communication occurs through chemical messages in a process called signal transduction. The purpose of these signals is to tell the cell what to do, such as when to grow, divide into two new cells, and die. Targeted cancer therapies use drugs that block the growth and spread of cancer by interfering with specific molecules involved in carcinogenesis (the process by which normal cells become cancer cells) and tumor growth. By focusing on molecular and cellular changes that are specific to cancer, targeted cancer therapies may be more effective than current treatments and less harmful to normal cells. Exciting results have come from studies of multitargeted tyrosine kinase inhibitors, "small" molecules that act on multiple receptors in the cancerous cells, like Tyberb and Sutent. Targeted "small-molecule" therapies ruled at the recent annual ASCO meeting of oncologists. The trend is away from the monoclonals to the small molecules, a trend in which a new predictive test may be able to hasten. The EGRFx (TM) assay is able to test molecularly-targeted anti-cancer drug therapies like Iressa, Tarceva, Tykerb, Sutent and possibly Nexavar, because of being small molecules. The EGFRx (TM) assay 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 (cell metabolism) and morphologic (structure) endpoints, at the cell "population" level (rather than at the "single cell" level). 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. Whole Cell Profiling measures genes before and after drug exposure. Gene Expression Profiles measures the gene expression only in the "resting" state, prior to drug exposure. Not only is this an important predictive test, 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. Laboratory screening of samples from a patient's tumor can help select the appropriate treatment to administer, avoiding ineffective drugs and sparing patients the side effects normally associated with these agents. Under this approach, scientists study how an individual's cancerous cells respond to several drugs. Doctors have learned that even when the disease is the same type, different patients' tumors respond differently to chemotherapeutic drugs. More and more physicians and patients are turning to individualized therapies to treat cancers. Without individualized testing, it's difficult to determine which drugs are best for patients who don't respond to standard therapies. Assay-directed chemotherapy is an individualized approach to killing cancer. A method used to determine what precise medications would kill the particular cancer. Doctors have assumed that stopping cell division would stop cancer, because most cancer cells divide and grow rapidly. But the approach didn't always kill the malignant cells. Cancer isn't a case of cells growing out of control, but of cells refusing to die on schedule. Assay testing can provide predictive information to help physicians choose between chemotherapy drugs, eliminate potentially ineffective drugs from treatment regimens and assist in the formulation of an optimal therapy choice for each patient. This can spare the patient from unnecessary toxicity associated with ineffective treatment and offers a better chance of tumor response resulting in progression-free survival. Preponderance of currently-available evidence argues persuasively in favor of the use of the assays. Gdpawel Wed, 20 Sep 2006 00:00:00 GMT