Oncologic In Vitro Chemoresponse Assays

[gpawelski]

Patients, physicians, insurance carriers, and the FDA are all calling for predictive tests that allow for rational and cost-effective use of chemotherapeutic 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 assays for optimized use of medical treatment of malignant disease.

Researchers have seen that whether a tumor was a breast tumor, prostate tumor, lung tumor or lymphoma, 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 brain, prostate, lymphoma 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.

Conventionally, oncologists make chemotherapy treatment recommendations on the basis of published reports of clinical trials and a patient's health status and treatment preferences in choosing chemotherapy regimens. But the statistical results of these population-based studies might not apply to an individual. For many cancers, more than one standard treatment exists. Physicians select drugs based on their personal experience, possible side effects and the patient's condition, among other factors. However, the system is overloaded with drugs and underloaded with wisdom and expertise for using them.

In patients with cancer, it is often difficult to select an effective treatment because the tumor develops resistance to many drugs. Currently, physicians select an empirically-selected drug and must wait about six months to see whether it is effective on a particular patient. For many cancers, especially after a relapse or when a particular treatment is ineffective, more than one standard treatment exists.

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. You might kill off a whole lot of cancer, only to cause a mutation in the remaining cancer, such that the remaining cancer behaves in a more aggressive fashion.

Cancers that are a product of these genetic mutations release cells from the usual controls of proliferation and survival, making them so much harder to fight it. Following this mutation, the cancer cells acquire the ability to proliferate without the normal restraints. As the cancer grows, it may infiltrate and destroy the surrounding tissue, and metastasize by penetrating into blood vessels, lymph nodes, and body cavities. Distant metastasis via the bloodstream may affect virtually any organ (the lungs, bones, liver, adrenals, and even the brain).

There are patients who have progressive disease after first-line therapy, only to enjoy a dramatic benefit from second or even third line therapy, and these patients would have been much better served by receiving the most probable active treatment the first time around. By utilizing cell culture assays, oncologists can choose the treatment which is most likely to work or that is what their patients want.

With cell culture assays, 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.

Cell culture assays are 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. These assays 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 cell culture 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. However, some assays 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.

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. 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 narrow indication. But these drugs may have many useful applications, and a cell culture assay offers a way of seeing if any of these new drugs might apply to your specific cancer.

A cell culture 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.

In studies, patients treated with drugs "active" in the assays had a higher response rate than the entire group of patients as a whole. Patients treated with drugs "inactive" in the assays had lower response rates than the entire group of patients. 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.

Both fluid and solid tumor (200mg or 10mm 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 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. Some 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. 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.

These cell culture assays are not intended to be scale models of chemotherapy in the patient, anymore than the barometric pressure is a scale model of the weather. But it's always more likely to rain when the barometer is falling than when it is rising, and chemotherapy is more likely to work in the patient when it kills the patient's cancer cells in the laboratory. It is no different than any other medical test in this regard.

These tests have been extensively validated for "accuracy," without any controversy whatsoever. In more than 40 peer-reviewed publications, in a wide range of human tumors, ranging from acute and chronic leukemia to ovarian and breast cancer, patients treated with drugs which were active in the assays were more likely to respond to treatment than the group as a whole and dramatically more likely to respond to treatment than patients treated with drugs which were not active in the assays, with there being a 7 to 9 fold advantage to treatment with assay "positive" drugs, compared to assay "negative" drugs. In a number of studies, patients treated with assay "positive" drugs enjoyed significant survival advantages, as well.

The criteria always used to evaluate medical tests is the "accuracy" of the tests and not the "efficacy" of the tests. There is no single test (laboratory or radiographic or anything else) used in cancer which has been proven to be "efficacious" in prospective randomized trials, where patients are managed with and without the benefit of the information provided by the tests, and treatment outcomes compared. The only information which has ever been obtain is how accurate the tests are, and the accuracy of the cell culture assays compares favorably with that of other similar tests used in cancer medicine. Critics of the testing are demanding a standard of proof which is truly unprecedented, and which has not been met by all of the other tests used in cancer medicine.

The test is showing the "effaciousness" of a particular drug, the test itself doesn't have to show it is "effacious." It just has to show it is "accurate" to standards set by the FDA. Most of the cancer treatments used have not met the standard of proof demanded of a cell culture assay, which is a test and not a treatment. The degree to which "standard" cancer chemotherapy has been "proven" to be more efficacious than other forms of treatment has been overstated, overassumed, and over-sold.

Having some foreknowledge of a given chemo agent's expected result before its administration would benefit the individual patient. The cost of drugs is enormous. Patients are followed with serial CT scans, MRI's and even Pet Scans, just to see if a tumor is growing or shrinking. Not to mention the hospitalizations for toxicity, bone marrow tranfusions, etc. The point is, the cost of ineffective therapy is truly enormous and all cell culture assays are particularly good at identifying ineffective therapy, and some are good at identifying effective therapy. The biggest criticism of cell culture assays is its standard for proving its value - improving overall survival.

http://weisenthalcancer.com/Patient%20P ... kFacts.htm

[Guest bean_si (Not Active)]

I had a PET/CT scan yesterday and have the CD of that scan. While it is terrifying and upsetting, I am fascinated by the technology.

The CT image shows as a kind of x-ray - picking up more dense tissue, especially the bones. The abnormalities are difficult for a layperson to see.

Then they show the PET image which seems fuzzy and consisting of internal organs. Certain areas are shown as black.

Then you have the fused image which is mostly a blue image. In this image, the area that barely showed in the CT scan and showed as black in the PET scan, now show as yellow-gold and are much more easy to see. And yet for the most part, I can't make a determination as a layperson even though it seems that I have a half dozen "lit up" areas.

The only one that stands out is the lung tumor.

Now on the fused image you can see where the tumor was. It shows a faint impression of the entire tumor - a half moon faintly lit image on the left side (facing me) which is probably inflammation/macrophage activity, a central area which appears to be necrotic and a definite and even (fairly) large border on the right side of the tumor which appears to be malignant. This area abuts or perhaps even invades the lymph area in the center.

The other images that I see are lit up but more fuzzy, several correspond to areas where I have had trouble. These could indicate inflammation rather than cancer.

I hope.

Cat

[Elaine]

Good Morining Cat,

You sound more optimistic today, a guarded optimism, which is the best kind to have given our circimstances, huh? Hey, is there anyway for you to download the image to someplace where we could see it too? Do you have a web page or something?

I am always fascinated by what you write and you don't scare me a bit!

love

elaine

[Guest bean_si (Not Active)]

Elaine

I did put them up and sent you the link. I hesitate to post that link here for a few hundred reasons, one of which is my privacy. Another is that I doubt any of us, including me, could absolutely correctly interpret them.

Of course, I'm positive I interpreted them right and there is still cancer in the lung mass. Although I generally get the report directly from the hospital the next morning, I was told that it takes a specialist to interpret them and I may have to wait until Monday.

If anyone else is going through a PET/CT scan or is intellectually inquisitive about the way they operate, please drop me a private message to get the link. It is pretty interesting. The first image is CT scan. The second PET scan and the third fused scan. I have no idea what the heck the fourth image is. Maybe it's a Rosach ink blot test.

[gpawelski]

Good review papers exist on cell culture assays and are increasingly appreciated, understood and applied by the private sector and European clinicans and scientists. The literature on these assays have not been understood by many NCI investigators and by NCI-funded university investigators, because their knowledge was almost always geared towards an assay technique (cell-growth) that hasnt' been used in private labs for over fifteen years now.

NCI studies never determine if "fresh" tumor assays worked. All of the considerable literature which supports the use of these assays in patient management has been based on true "fresh" tumor (non-passaged) cell assays.

Some years ago, NCI made an attempt to study "assay-directed" therapy of lung cancer. The study was a failure because it was done with established permanent cell lines (instead of fresh cells), which have been conclusively proven to have no predictive value at all with respect to the clinical activity spectrum. The result was a dismal 11% response.

The NCI used "cell lines" because the major expertise of the investigators who carried out any study was in the creation of cancer cell lines, and they wanted to see if they could perform assays on these cell lines to use in patient therapy. The results showed they were able to test successfully only 22% of specimens received, including only 7% of primary lesions.

This contrasts with a 75% overall success rate reported by earlier investigators who used the same assay system in "fresh" tumor and a routinely obtained >95% success rate using improved (cell death) methods available today.

The NCI spent $15 million on a single-cell suspension "fresh" tumor assay with cell proliferation (cell growth) rather than cell death as an endpoint. When that didn't work, they folded their hand and specifically discouraged future applications of cell culture testing in their grant and contract guidelines, dating from the late 1980's. They never supported any drug development work based on primary cultures of three dimensional cell clusters with cell death endpoints, which very nicely recapitulate known disease specific activity endpoints.

Then later, there were sophisticated programs to discover gene expression microarrays which predict for responsiveness to drug therapy. The NCI has a huge lab working on microarrays to look for patterns of mRNA and protein expression which are predictive of chemotherapy response. They spent 2 years trying to find patterns which correlated using the NCI's various established ovarian "cell lines."

They thought they had something, but when they started to apply them to "fresh" tumor specimens, none of the results in the "cell lines" was applicable to the "fresh" tumors. Everything they worked out in the "cell lines" was not worth anything and they had to start over from square one.

However, the limitations and non-applicability of the NCI efforts, failed to realize that the way to identify informative gene expression patterns is to have a "gold standard" and the (cell-death) cell culture assays are by far the most powerful, efficient, useful "gold standard" to have, adding the potential value of the assays to individualize cancer therapy.

It was routine for the NCI to append statements to grant and contract initiative announcements that applications relating to cell culture assays were strongly discouraged. Dr. Dan Von Hoff published a paper around 1990 in which he stated that clinical trials of cell culture assays would never be supported. And the cooperative groups have utterly refused to do the studies. Why should they? Five times as much work for much less (financial) reward.

There was an enormous amount of published, peer-reviewed research documenting the "accuracy" of cell culture assays. Scores of studies in thousands of patients. Based on both response and survival, but all of it excluded from the ASCO and insurance industry reviews. And it's the only evidence existing to validate any other medical test used as an aid in drug selection.

Disallow the introduction of published, peer-reviewed evidence documenting accuracy. While allowing the introduction of hearsay, unstated, undocumented, undescribed, unpublished, unpeer-reviewed non-evidence.

And the fact that "proving" efficacy in one situation would do nothing to prove efficacy in any other situation. This is why the FDA demands clinical trials data showing efficacy for each and every indication relating to drugs.

Let's say a plan assay-directed clinical trial in relapsed NSCLC proves efficacy. All we prove is that it improves things for one small indication. Relapsed NSCLC, not ovarian cancer. And it gets worse. The year after the close of the study, two new drugs become available and the assay-directed clinical study only proves efficacy with the old drugs. It doesn't prove efficacy involving the new and improved drugs. A constantly moving target. So then you say, just go out and get a grant to do another one.

[jcawork]

Who wrote this? Is this a quote?

"In patients with small-cell lung cancer, it is one of the very few forms of carcinoma for which chemotherapy has some positive effect on survival, but the effect is measured in terms of weeks or months, not years. Small-cell lung cancer tends to metastasize readily and grow rapidly. It is also believed that surgery may leave behind some stray cancer cells, which depends on the thoracic surgical oncologist involved."

[gpawelski]

Came from the January 10, 2002 issue of the New England Journal of Medicine

[gpawelski]

Medicare Contractor Establishes Reimbursement Coverage Policy for Cell Culture Assay Tests

National Heritage Insurance Company (NHIC), the contractor that administers Medicare programs in California, has established a positive coverage policy for Cell Culture Assay Tests known as Chemosensitivity (Resistance) Testing or Oncologic In Vitro Chemoresponse Assays for a tumor specimen from a Medicare patient obtained anywhere within the United States, but submitted for testing by one of the approved laboratories located within Southern California. Medicare bills for this testing are billed through NHIC because the test is conducted by the approved laboratories in California.

This pre-test can help see what treatments have the best opportunity of being successful for "high" risk cancer patients. The test measures the response of "live" tumor cells to drug exposure. Following this exposure, the assays measure both cell metabolism and cell morphology (Functional Profiling). The integrated effect of the drugs on the whole cell, resulting in a cellular response to the drug, measuring the interaction of the entire genome. Assays based on "cell-death" occur in the entire population of tumor cells.

This cell culture assay technology has been clinically validated for the selection of optimal chemotherapy regimens for individual patients. It is a laboratory analysis based on tumor tissue profiling that uses "fresh" human tumor biopsy or surgical specimen to determine which drugs or combinations of chemotherapeutic agents have the highest likelihood of response for individual cancer patients.

Following the collection of "fresh" tumor cells obtained from surgery or tru-cut needle biopsies, a cell culture assay is performed on the tumor sample to measure drug activity (sensitivity and resistance). This will pinpoint which drug(s) are most effective. Tissue, blood, bone marrow, and ascites and pleural effusions are possibilities, providing tumor cells are present. At least one gram of fresh tissue is needed to perform the tests, and a special kit is obtained in advance from the lab. The treatment program developed through this approach is known as assay-directed therapy.

Individualized assay-directed therapy is based on the premise that each patient's cancer cells are unique and therefore will respond differently to a given treatment. This is in stark contrast to standard or empiric therapy, which chemotherapy for a specific patient is based on average population studies from prior clinical trials.

The decision had been made that the assay is a perfectly appropriate medical service, worthy of coverage on a non-investigational basis. What is of particular significance is that they abandoned the artificial distinction between "resistance" testing and "sensitivity" testing and are providing coverage for the whole FDA-approved kit. Drug "sensitivity" testing is merely a point a little farther along on the very same continuum which "resistance" testing resides.

Cell cuture assay tests based on "cell-death" have proven very effective in identifying novel treatment combinations for a variety of cancers. The value of cell-death assays is that they can and do accurately predict clinical outcomes and define novel chemotherapeutic synergies. It can help see what treatments will not have the best opportunity of being successful (resistant) and identify drugs that have the best opportunity of being successful (sensitive).

The current clinical applications of in vitro chemosensitivity testing is ever more important with the influx of new "targeted" therapies. Given the technical and conceptual advantages of "functional profiling" of cell culture assays together with their performance and the modest efficacy for therapy prediction on analysis of genome expression, there is reason for renewed interest in these assays for optimized use of medical treatment of malignant disease.

The payment provided will be sufficiently realistic that all Medicare patients for whom this testing is indicated will be able to get it with only the routine 20% co-payment, as Medi-gap insurance secondaries are mandated to provide payment for co-pays for Medicare-approved services.

The coverage became effective for claims for services performed on or after February 19, 2007. The decision is posted at:

http://www.medicarenhic.com/cal_prov/ar ... t_0107.htm

NHIC Medicare Services reimburses qualified laboratories in Southern California for cell culture assay tests on a Medicare patient anywhere in the United States.

Likewise, Highmark Medicare Services reimburses a qualified laboratory in Pennsylvania for cell culture assay tests on a Medicare patient anywhere in the United States.

NHIC has jurisdiction over Southern California, so that is who gets billed when the laboratory is located in California.

Highmark has jurisdiction over laboratories in Pennsylvania, so that is who gets billed when the laboratory is located in Pennsylvania.

The coverage decision is posted at:

http://www.highmarkmedicareservices.com ... 32007.html

[gpawelski]

These cellular-based pre-tests can report prospectively to a physician specifically which chemotherapy agent would benefit a cancer patient by testing that patient’s "live" cancer cells. One gets more accurate information when using intact RNA isolated from "fresh" tissue than from using degraded RNA, which is present in paraffin-fixed tissue.

A "fresh" sample tumor can be obtain from surgery or biopsy (Tru-cut needle biopsies). For newly diagnosed patients, the test is most reliable before a tumor has been exposed to chemotherapy. However, patients that have failed previous chemotherapy treatment, the test still can be done once a patient waits at least four weeks. A FDA-approved kit is obtained from the lab for the surgeon or pathologist.

Good review papers exist on cell culture assays and are increasingly appreciated, understood and applied by the private sector and European clinicans and scientists. The literature on these assays have not been understood by many NCI investigators and by NCI-funded university investigators, because their knowledge was almost always geared towards an assay technique (cell-growth) that hasnt' been used in private labs for over fifteen years now.

NCI studies never determine if "fresh" tumor assays worked. All of the considerable literature which supports the use of these assays in patient management has been based on true "fresh" tumor (non-passaged) cell assays.

Some years ago, NCI made an attempt to study "assay-directed" therapy of lung cancer. The study was a failure because it was done with established permanent cell lines (instead of fresh cells), which have been conclusively proven to have no predictive value at all with respect to the clinical activity spectrum. The result was a dismal 11% response.

The NCI used "cell lines" because the major expertise of the investigators who carried out any study was in the creation of cancer cell lines, and they wanted to see if they could perform assays on these cell lines to use in patient therapy. The results showed they were able to test successfully only 22% of specimens received, including only 7% of primary lesions.

This contrasts with a 75% overall success rate reported by earlier investigators who used the same assay system in "fresh" tumor and a routinely obtained >95% success rate using improved (cell death) methods available today.

The NCI spent $15 million on a single-cell suspension "fresh" tumor assay with cell proliferation (cell growth) rather than cell death as an endpoint. When that didn't work, they folded their hand and specifically discouraged future applications of cell culture testing in their grant and contract guidelines, dating from the late 1980's. They never supported any drug development work based on primary cultures of three dimensional cell clusters with cell death endpoints, which very nicely recapitulate known disease specific activity endpoints.

Then later, there were sophisticated programs to discover gene expression microarrays which predict for responsiveness to drug therapy. The NCI has a huge lab working on microarrays to look for patterns of mRNA and protein expression which are predictive of chemotherapy response. They spent 2 years trying to find patterns which correlated using the NCI's various established ovarian "cell lines."

They thought they had something, but when they started to apply them to "fresh" tumor specimens, none of the results in the "cell lines" was applicable to the "fresh" tumors. Everything they worked out in the "cell lines" was not worth anything and they had to start over from square one.

However, the limitations and non-applicability of the NCI efforts, failed to realize that the way to identify informative gene expression patterns is to have a "gold standard" and the (cell-death) cell culture assays are by far the most powerful, efficient, useful "gold standard" to have, adding the potential value of the assays to individualize cancer therapy.

National Heritage Insurance Company found that even back in 1999, the Medicare Advisory Panel concluded that cell culture assay tests offered "clinical utility." After listening to detailed clinical evidence, the Medicare Coverage Advisory Committee (MCAC) found that these assay systems can aid physicians in deciding which chemotherapies work best in battling an individual patient's form of cancer.

MCAC's laboratory and diagnostic services panel heard presentations from experts regarding the clinical data associated with the assay systems. The panel questioned presenters carefully on clinical performance, study findings, literature analyses, and patient impact of the tests. After considering the evidence, the panel conclued that the tests demonstrated clinical utility for directing therapy.

Although Medicare had been reimbursing for cell culture drug "resistance" tests since 2000, it wasn't until the beginning of this year they abandon the artificial distinction between "resistance" testing and "sensitivity" testing and are providing coverage for the whole FDA-approved kit.

[gpawelski]

It amazes me not only that some private insurance carriers don't like to pay for cell culture assay tests but that they don't emphatically mandate it as a requirement for obtaining chemotherapy reimbursement against ill-directed treatments.

The validation standard that private insurance companies is accepting from "molecular" profiling tests is "accuracy" and not "efficacy." The "bar" has been instantly lowered. No longer will it be essential to prove that the use of a diagnostic test improves clinical outcomes, all they have to do for these "molecular" profiling tests is prove that the test has a useful degree of "accuracy." However, at the same time, the validation standard they want for "cell-based" profiling tests is "efficacy."

The "cell-based" profiling tests have the same entitlement to be judged by the same validation standard as "molecular" profiling tests. The combination of measuring morphologic (structural) effects and metabolic (cell metabolism) effects constitutes measuring the "profile" at the whole cell level. It must be noted that both types of dignostic tests are just that, "tests" and not treatment.

Profit, as we have seen, is a powerful motivating force. Among the private payors, at least, the profit motive is entirely consistent with the goal of the test, which is to identify efficacious therapies irrespective of drug mark-up rates.

The evidence in support of these assays is more than sufficient to justify the funding of validation trials, if any more truly are needed, as claimed - speciously and self-servingly - by the medical establishment.

Everyone is scared to death - and rightly so - at what is going to happen to the healthcare economic system with the introduction of increasingly expensive new drugs that benefit only a small percentage of patients who receive them, hence the headlong rush to develop tests to identify molecular predisposing mechanisms whose presence still does not guarantee that a drug will be effective for an individual patient.

Nor can they, for any patient or even large group of patients, discriminate the potential for clinical activity among different agents of the same class, such as Sutent, Tarceva, Iressa, and Nexavar.

The FDA could benefit too, as they find themselves under increasing pressure to allow new drugs into marketplace while at the same time protecting the safety of potential recipients of those drugs as well as the financial interests of those who will have to pay for them.

It explains the new paradigm of requiring a companion diagnostic as a condition for approval of new targeted therapies. The pressure, in fact, is so great that the companion diagnostics they've approved often have been mostly or totally ineffective at identifying clinical responders (durable and otherwise) to the various therapies.

I think that in both of these areas - private insurance carriers and the FDA - there is a very real opportunity to make a substantial impact and contribution, an interest in saving the healthcare system perhaps billions of dollars a year (and thereby the healthcare system itself) by ensuring that expensive treatments are used appropriately.

Committee chairpersons, committee members and persons in congress who may have personal interests not only in discovering new cancer treatments - everybody wants that - but also, in the "here and now," using currently-available cell culture assay technologies to improve the effectiveness of existing drugs and save lives today by administering the right drug to the right patient at the right time.