1. The needed change in the "war on cancer" will not be on the types of drugs being developed, but on the understanding of the drugs we have. The system is overloaded with drugs and underloaded with the wisdom and expertise for using them.

Cancer patients usually undergo four or five courses of chemotherapy before medical oncologists can tell whether the treatment is having an effect. By that time, the tumor may have grown so large that it is too late to switch to another chemotherapy regimen or the patient may be so weakened by the treatment that trying another approach is not immediately feasible. Medical oncologists treat a lot of patients but they don't know going into treatment if it's going to work.

A major obstacle in controlling cancer growth and metastasis in patients is the widespread inappropriate use of anti-cancer drugs. As the increasing numbers and types of anti-cancer drugs are developed, oncologists become more and more likely to misuse them in their practice. Between 2002 and 2004, 395 cancer drugs were submitted for clinical trials.

It would be highly desirable to know what drugs are effective against your particualr cancer cells before these cytotoxic agents are systemically administered into your body. Cell culture assays are tests on living specimens of cancer cells to determine the optimal combination of chemotherapy drugs. These assays are specifically tailored for each individual patient, with no economic ties to outside healthcare organizations, and recommendations are made without financial or scientific prejudice.

Recommendations are designed scientifically for each individual patient. Various assays are performed on a tumor sample to measure drug activity (sensitivity and resistance). This will determine no only what drug(s) will not effectively work, but which drug(s) will be most effective for your cancer. Then a treatment recommendation is developed through what is know as "assay-directed" therapy.

At one time, chemosensitivity testing was considered unreliable because it was only fifty percent accurate and it took too long to get the results. Today, preliminary results are completed in about seven days and chemosensitivity testing has progressed to the point where it is

Posted at 3:05PM on Jun 7th 2006 by Gregory D. Pawelski

2. greater than 90% effective.

The key to improving drug sensitivity tests is related to the number and types of drugs tested. The more anti-cancer drug types there are in the selective arsenal, the more likely the system is to prove beneficial. In order to acquire sufficient data, tumors are tested with at least two assay endpoints, and most often three, for sensitivity in any one patient. On average, up to twenty drugs and combinations at two concentrations in three different assay systems, is an effective way to avoid false-positive or false-negative data. Careful choice of drug doses and administration intervals also improves outcomes.

Conventionally, chemotherapy is prescribed by medical oncologists according to fixed schedules. These schedules are standardized drug regimens that correspond to specific cancer by type or diagnosis. These schedules, developed over many years of clinical trials, assign patients to the drugs for which they have the greatest statistical probability of response.

However, patients with cancers that exhibit drug resistance are on the wrong side of the probability curve. They will likely receive treatments that are wrong for them. A failed attempt at chemotherapy is detrimental to the physical and emotional well-being of patients, financially burdensome, and may preclude further effective therapies.

Every cancer patient should have his/her own unique chemotherapy trial based on consultation of pathogenic profiles and drug sensitivity testing data. Research and application of drug sensitivity assays are being encouraged by growing patient demands, scientific advances and medical ethics. Drug sensitivity tests are not a luxury but an absolute necessity, and a powerful strategy that cannot be overlooked.

A chemo-induced gene mutation can happen when the original chemo received does not work. The cancer comes back. When it does this, the cancer comes back more aggressively. The mutagenic effects (changes in form) of chemotherapy on a genetically-unstable tumor, drives the tumor into a state of more aggressive behavior.

A cell culture assay uses your living tumor cells to determine which drug or drug combination induces apoptosis (cell death) in the laboratory. Each patient is highly individualized with regard to sensitivity to chemotherapy drugs. A patient's responsiveness to chemotherapy has its own unique individuality.

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 may take years to find out. Cell culture assay testing offers a way of seeing if any of these new drugs might apply to your specific cancer.

Posted at 7:46PM on Jun 7th 2006 by Gregory D. Pawelski

3. The greatest problem associated with cancer drugs is the same as with any drugs: the greed of drug companies. They are going to develop only drugs that are patentable which is to say they are going to throw away the hundreds of millions of years of wisdom that Mother Nature has accumulated simply because you cannot patent those treatments. Many such once promising cancer treatments were not only abandoned but outright banned. Drug business is second in profitability only to the arms industry.

Posted at 6:24AM on Jun 8th 2006 by Hedi Hegyi

4. What are some examples of "cell culture assay" tests? Is this like a FISH test?

Posted at 2:23PM on Jun 8th 2006 by Evan Adams

5. Cell culture assay tests are laboratory tests used in the selection of treatments for cancer patients. This includes estrogen receptor, progesterone receptor, Her2/neu, immunohistochemical staining for tumor classification, bacterial culture and sensitivity testing, CT, MRI and Pet Scans to measure tumor response to treatment, EGFR amplification/mutation, and Oncotype DX. The traditional criteria ever used to evaluate laboratory tests has been the predictive "accuracy" of these tests.

Cell culture assays are not used to test one chemotherapeutic regimen against another, that's what randomized prospective clinical trials are for, to establish clinical "efficacy" of a drug (tumor response). Cell culture assay tests have been well proven to have predictive "accuracy" with that of estrogen receptor, progesterone receptor, Her2/neu and the newer molecular tests.

In light of the precious little in the way of guidance from clinical trials with respect to best empiric therapy and the importance of basing cancer treatment at least in part on patient preferences, it is entirely reasonable to support judicious application of laboratory tests which have been well characterized with respect to test "accuracy." This is a diagnostic test and should be held to that criteria, and not to that of therapy.

All available assay tests 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 assay tests are also 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.

There are a family of assays based on the concept of total cell kill, or cell death occurring in the entire popluation of tumor cells. The general measurements of cell death are the DISC assay method, the MTT assay method, the ATP assay method, and the flurescein diacetate assay method. These four endpoints produce valid and reliable measurements of cell death. They also correlate well with each other on direct comparisons of the different methods.

Posted at 10:24PM on Jun 8th 2006 by Gregory D. Pawelski