When a patient has an infection, doctors often send a sample of infected blood or tissue to a lab where they can grow the bacteria and see which antibiotics are most effective (called Bacterial Culture and Sensitivity Testing). Chemosensitivity testing is an attempt to do something similar for cancer; fresh samples of the patient's tumor from surgery or a biopsy are grown in test tubes and tested with various drugs. Drugs that are most effective in killing the cultured cells are recommended for treatment. It is highly desirable to know what drugs are effective against your particular cancer cells before highly-toxic agents are systemically administered to your body.
One approach to individualizing patient therapy is chemosensitivity testing. Chemosensitivity assay is a laboratory test that determines how effective specific chemotherapy agents are against an individual patient's cancer cells. Often, results are obtained before the patient begins treatment. This kind of testing can assist in individualizing cancer therapy by providing information about the likely response of an individual patient's tumor to proposed therapy. Chemosensitivity testing may have utility at the time of initial therapy, and in instances of severe drug hypersensitivity, failed therapy, recurrent disease, and metastatic disease, by providing assistance in selecting optimal chemotherapy regimens.
All available chemosensitivity assays are able to report drug 'resistance' information. Resistance implies that when a patient's cancer cells are exposed to a particular chemotherapy agent in the laboratory, the cancer cells will continue to live and grow. Some chemosensitivity assays also are able to report drug 'sensitivity' information. Sensitivity implies that when a patient's cancer cells are treated with a particular chemotherapy agent in the laboratory, that agent will kill the cancer cells or inhibit their proliferation.
The goal of all chemosensitivity tests is to determine the response of a patient's cancer cells to proposed chemotherapy agents. Knowing which chemotherapy agents the patient's cancer cells are resistant to is important. Then, these options can be eliminated, thereby avoiding the toxicity of ineffective agents. In addition, some chemosensitivity assays predict tumor cell sensitivity, or which agent would be most effective. Choosing the most effective agent can help patients to avoid the physical, emotional, and financial costs of failed therapy and experience an increased quality of life.
Fresh samples of the patient's tumor from surgery or a biopsy are grown in test tubes and tested with various drugs. Drugs that are most effective in killing the cultured cells are recommended for treatment. Chemosensitivity testing does have predictive value, especially in predicting what 'won't' work. Patients who have been through several chemotherapy regimens and are running out of options might want to consider chemosensitivity testing. It might help you find the best option or save you from fruitless additional treatment. Today, chemosensitivity testing has progressed to the point where it is 85% - 90% effective.
Conventionally, oncologists rely on clinical trials in choosing chemotherapy regimens. But the statistical results of these population-based studies might not apply to an individual. For many cancers, especially after a relapse, more than one standard treatment exists. There is rarely a situation where you would get everyone to agree that there's only one form of therapy. Physicians select drugs based on their personal experience, possible side effects and the patient's condition, among other factors. The system is overloaded with drugs and underloaded with wisdom and expertise for using them.
Chemosensitivity testing might help you find the best option, or save you from fruitless additional treatment. Another situation where chemosensitivity testing might make particularly good sense is in rare cancers where there may not be enough experience or previous ideas of which drugs might be most effective.
Finally, there has been a veritable deluge of new approvals of cytotoxic drugs in recent years as the tortuous FDA process has been speeded and liberalized. In many cases a new drug has been approved on the basis of a single very very narrow indication. But these drugs may have many useful applications - and it's going to take years to find out. Chemosensitivity testing offers a way of seeing if any of these new drugs might apply to your specific cancer.
Another Name
Cell Culture Drug Resistance Testing (Chemotherapy Sensitivity and Resistance Assays) refers to laboratory testing of a patient's own cancer cells with drugs that may be used to treat the patient's cancer. A group of lab tests known as human tumor assay systems (HTAS) can aid oncologists in deciding which chemotherapies work best in battling an individual patient's form of cancer. The assay is a lab test performed on a biopsy specimen containing living cancer cells. It's used to determine the sensitivity or resistance of malignant cells to individual chemotherapy agents. Depending on how well the tumor cells respond to each chemotherapy agent, they are rated as sensitive, resistant or intermediate to chemotherapy. The concept is that you are better off using a chemotherapy drug that your tumor reacts to strongly than one your tumor resists.
There have been over 40 publications in peer-reviewed medical literature showing correlations between cell-death assay test results and the results of clinical chemotherapy in more than 2,000 patients. In every single study, patients treated with drugs active in the assays had a higher response rate than the entire group of patients as a whole. In every single study, patients treated with drugs inactive in the assays had lower response rates than the entire group of patients. In every single study, patients treated with active drugs were much more likely to respond than patients treated with inactive drugs, with assay-active drugs being 7 to 9 times more likely to work than assay-inactive drugs. A large number of peer-review publications also reported that patients treated with assay-tested 'active' drugs enjoyed significantly longer survival of cancer than patients with assay-tested 'negative' drugs.
Listing of 'Reputable' Labs USA:
These labs will provide you and your physician with in depth information and research on the testing they provide.
Analytical Biosystems, Inc., Providence, Rhode Island. 1-800-262-6520
Anticancer, Inc., San Diego, CA. 1-619-654-2555
Cancer Therapeutics, Inc., Thomasville, GA. 1-229-224-6839
DiaTech Oncology, Brentwood, TN. 1-615-294-9033
Genomic Health, Inc. Redwood City, CA. 1-650-556-9300
Genoptix, Inc., San Diego, CA 1-858-523-5000
Human Tumor Cloning Laboratory, San Antonio, TX. 1-210-677-3827
Impath, Inc., New York, NY. 1-800-447-8881
Nu Oncology Labs, Virginia Beach, VA. 1-757-554-0926
Oncotech, Inc., Irvine, CA. 1-714-474-9262 / FAX 1-714-474-8147
Oncovation LLC, New York, N.Y. 1-212-514-2422
Precision Therapeutics, Pittsburgh, PA. 1-866-243-6639
Rational Therapeutics Institute, Long Beach, CA. 1-562-989-6455
Sylvester Cancer Institute, Miami, FL. 1-305-547-6875
Weisenthal Cancer Group, Huntington Beach, CA. 1-866-364-0011
How May a Patient Arrange to Have Their Tumor or Leukemia Tested?
Both fluid and solid tumor (200mg in size) specimens may be sent out via Federal Express or another overnight courier service for testing at one of more than a dozen labs around the country. Note that the choice of a lab is not a geographical consideration, but a technical consideration. All of the labs that are listed are experienced and capable of providing very useful information. However, the labs vary considerably with regard to technologies, approach to testing, what they try to achieve with the testing, and cost. These private laboratories have been offering these assays as a non-investigational, paid service to cancer patients, the average cost being about $2,000, in a situation where 20 different drugs and combinations are tested, at two drug concentrations in three different assay systems.
Assay-tests could be performed from ovarian cancer cells in pleural fluid (fluid from the cavity that surrounds the lungs) which is evidence of Stage IV ovarian cancer, or from Ascites (an abnormal accumulation of fluid in the abdomen), and of course lymph nodes. A worse case scenario is the spinal fluid (spinal tap) but only to diagnose Leptomeningeal Carcinomatous (ovarian). The labs will provide you and your physician with in depth information and research on the testing they provide.
By investing a little time on the phone speaking with the lab directors, you should have enough knowledge to present the concept to the patient's own physician. At that point, the best thing is to ask the physician, as a courtesy to the patient, to speak on the phone with the director of the laboratory in which you are interested, so that everyone (patient, physician, and laboratory director) understand what is being considered, what is the rationale, and what are the data which support what is being considered.
Some Resistance
The fact that some doctors don't agree isn't stopping many cancer patients from taking this matter into their own hands, and sending their live path specimens off to one of the above private labs for assay-testing to be done. In fact, approximately 10,000 individual patient specimens are currently being submitted for testing by more than 1,000 clinical oncologists, surgeons and pathologists annually in the United States. There has been much discussion about whether assay (in vitro) tests are of any use, as the in vivo response to a drug may very well be different in the body than in the petri dish. But, they said the same for Bacterial Culture and Sensitivity Testing. Doctors cannot remember a time when they didn't have this technology. It is a 'gold' standard. So will Chemosensitivity Testing.
ADDENDUM POSTED June 2009
The drug discovery model over the last number of years has been limited to one gene/protein, one target, one drug. The 'cell' is a system, an integrated, interacting network of genes, proteins and other cellular constituents that produce functions. You need to analyse the systems' response to drug treatments, not just one target or pathway.
The decoding of the human genome in 2000, sparked hopes that a new era of tailored medicine was just around the corner. However, uncovering the genetic differences that determine how a person responds to a drug, and developing tests, or biomarkers, for those differences, is proving more challenging than ever. As a result, patients with cancer are still being prescribed medicines on a trial-and-error basis or one-size-fits-all.
The key to understanding the genome is understanding how cells work. The ultimate driver is 'functional' pre-testing (is the cell being killed regardless of the mechanism) as opposed to 'target' pre-testing (does the cell express a particular target that the drug is supposed to be attacking). While a 'target' test tells you whether or not to give 'one' drug, a 'functional' pre-test can find other compounds and combinations and can recommend them from the one test.
The core of 'functional' testing is the cell, composed of hundreds of complex molecules that regulate the pathways necessary for vital cellular functions. If a 'targeted' drug could perturb any one of these pathways, it is important to examine the effects of the drug within the context of the cell. Both genomics and proteomics can identify potential new thereapeutic targets, but these targets require the determination of cellular endpoints.
Cell-based functional pre-testing is being used for screening compounds for efficacy and biosafety. The ability to track the behavior of cancer cells permits data gathering on functional behavior not available in any other kind of testing.
Gene profiling tests, important in order to identify new therapeutic targets and thereby to develop useful drugs, are years away from working successfully in predicting treatment response for 'individual' patients. Perhaps this is because they are performed on dead, preserved cells that are never actually exposed to the drugs whose activity they are trying to assess.
It will never be as effective as the cell 'function' methodology, which has existed for the last twenty years and is not hampered by the problems associated with gene expression tests. That is because they measure the net effect of all processes within the cancer, acting with and against each other in real-time, and it tests 'living' cells actually exposed to drugs and drug combinations of interest.
It would be more advantageous to sort out what's the best 'profile' in terms of which patients benefit from this drug or that drug. Can they be combined? What's the proper way to work with all the new drugs? If a drug works extremely well for a certain percentage of cancer patients, identify which ones and 'personalize' their treatment. If one drug or another is working for some patients then obviously there are others who would also benefit. But, what's good for the group (population studies) may not be good for the individual.
Patients would certainly have a better chance of success had their cancer been 'chemo-sensitive' rather than 'chemo-resistant,' where it is more apparent that chemotherapy improves the survival of patients, and where identifying the most effective chemotherapy would be more likely to improve survival above that achieved with 'best guess' empiric chemotherapy through clinical trials.
It may be very important to zero in on different genes and proteins. However, when actually taking the 'targeted' drugs, do the drugs even enter the cancer cell? Once entered, does it immediately get metabolized or pumped out, or does it accumulate? In other words, will it work for every patient?
All the validations of this gene or that protein provides us with a variety of sophisticated techniques to provide new insights into the tumorigenic process, but if the 'targeted' drug either won't 'get in' in the first place or if it gets pumped out/extruded or if it gets immediately metabolized inside the cell, it just isn't going to work.
To overcome the problems of heterogeneity in cancer and prevent rapid cellular adaptation, oncologists are able to tailor chemotherapy in individual patients. This can be done by testing 'live' tumor cells to see if they are susceptible to particular drugs, before giving them to the patient. DNA microarray work will prove to be highly complementary to the parellel breakthrough efforts in targeted therapy through cell function analysis.
As we enter the era of personalized medicine, it is time to take a fresh look at how we evaluate new medicines and treatments for cancer. More emphasis should be put on matching treatment to the patient, through the use of individualized pre-testing.
Upgrading clinical therapy by using drug sensitivity assays measuring cell-death (apoptosis) of three dimensional microclusters of 'live' fresh tumor cell, can improve the situation by allowing more drugs to be considered. The more drug types there are in the selective arsenal, the more likely the system is to prove beneficial.
prepared by Gregory D. Pawelski from various Bio-Assay Journals GDPAWEL@comcast.net
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