Rational therapeutics

I am a patient of Dr. Nagourney at Rational Theraputics. I was diagnosed with stage 4 pancreatic cancer over a year ago. After several opinions, none to favorable, I chose Rational Theraputics because it seemed to offer the only hopeful alternative and the testing made sence. At present, My tumors are reduced to near normal and my tumor markers have been within normal rage for several months. Dr. Nagourney has been honest with me about my case and hopefully things will continue to go well in the future. I think you have to include Rational Theraputics as  one of you options.

Rational Therapeutics and Dr. Robert Nagourney's test saved my life.

I am a 69 year old physician. I was diagnosed with Stage 4 Renal Cell Ca July 1, 2010. The "standard" treatment, Sutent, did nothing for me. I required over 20 transfusions and was hospitalized for 6 weeks and not expected to live.

Dr. Nagourney's test is, to be blunt, a no-brainer: cancer cells are mixed with different chemotherapy drugs and if the cancer cells die, USE THAT DRUG.

In my case the test identified three drugs which never would have been prescribed for renal cell cancer. Within two weeks last fall they were working. My chest mets cleared. My kidney tumor has now been removed. My recent CT/PT is entirely negative. I haven't needed a transfusion in 6 months. I remain on the same three drugs.

Everyone with cancer and every doctor who deals with it should be sending tumor specimens to Rational Therapeutics or demanding that comparable testing - Chemosensitivity and Resistance Assay (CSRA) - be made available to them.

Have I overstated the case? Not on my life.

I am a 62 year old male who was first diagnosed with adenocarcinoma of the pancreas in mid 2003. At that time I was given a prognosis of 6 to 9 months. With the help of Dr. Nagourney and Rational Therapeutics I reached my 8- year survival anniversary on July 1, 2011. However, that is not the end of my story. On December 17, 2010, I was again diagnosed with a recurrant tumor on the body of my pancreas and underwent my second, albeit abridged, Whipple procedure. Rational Therapeutics was again there to assay the tumor and provide me with the correct chemo drugs. I am now 8 months post surgery and undergoing a three-drug regimine of chemotherapy. My CA 19-9 marker has been back in the normal range for over two months, my health is returning and I am re-gaining my weight. And so the answer to your question is that Rational Therapeutics and Dr. Nagourney make more than good sense. They get the results that you are seeking.

I am a 62 year old male who was first diagnosed with adenocarcinoma of the pancreas in mid 2003. At that time I was given a prognosis of 6 to 9 months. With the help of Dr. Nagourney and Rational Therapeutics I reached my 8- year survival anniversary on July 1, 2011. However, that is not the end of my story. On December 17, 2010, I was again diagnosed with a recurrant tumor on the body of my pancreas and underwent my second, albeit abridged, Whipple procedure. Rational Therapeutics was again there to assay the tumor and provide me with the correct chemo drugs. I am now 8 months post surgery and undergoing a three-drug regimine of chemotherapy. My CA 19-9 marker has been back in the normal range for over two months, my health is returning and I am re-gaining my weight. And so the answer to your question is that Rational Therapeutics and Dr. Nagourney make more than good sense. They get the results that you are seeking.

I was dx with stge IV lung cancer and brain mets 3 years ago. I am certain that I would not be alive and well today if I had not undergone testing by Rational Therapeutics. I had one chance to get chemo right the first time. With Dr. Nagourney's help I took that chance and we hit a bullseye! I have been in remission ever since.

It is critical to understand that there are BIG AND FUNDAMENTAL DIFFERENCES between the various tests being marketed.

Rational Therapeutics performs a "functional profile" chemosensitivity and resistance assay (CSRA). They require a fresh tissue sample, and then subject your live cancer cells to various chemos to determine which ones kill the most cells. This "functional" analysis looks at the "function" of live cells in the presence of chemo.

Other companies offer CSRA testing, however most use "cultured" cells from blood or needle biopsies or frozen tissue. From these samples they "clone" enough new cells to test. Unfortunately, cloned cells in isolation do not behave the same as fresh cells in their "native" state, and so these other CSRA tests are not very reliable.

Genetic tests, on the other hand, are all about "information", not "function". Decoding your "unique genetic makeup" may tell you what turned your cancer cells "on" or why they won't turn "off", but this only provides a better "target" at which to shoot chemo. Rather than shooting blindly (the old "standard protocol" way), a "molecular profile" (MP) improves your oncologist's ODDS of selecting the right arrow (treatment). Yet the treatment slected will still be based on statistics - what worked on other patients with similar molecular profiles - not necessarily what will kill YOUR cancer.

The Caris Target Now test is a DNA test that compares "the tumor's information with data from published clinical studies" to "help determine which treatments are likely to be most effective."

I believe genetic information is a GOOD thing. It is especially useful in drug development. But cancer, regardless of what's "written in our genes" lives and dies based on a multitude of other complex "functions" happening in our cells. And no matter how sophisticated or popular they are, gene tests CAN'T answer the ONLY question that is important to the individual cancer patient - "How does my cancer respond in the presence of chemotherapy? Does it die or not?"  

Historically the only way to find out was to subject the patient to round after round of treatment or let them be a guinea pig in a clinical trial. Now gene tests have fashioned better arrows. But the "functional profile" test performed by Rational Therapeutics goes straight to the bullseye first, and pulls out the right arrow without shooting the patient.

The only thing I can tell you about Caris is that the only truly useful information relates to the common markers which are tested in most pathology laboratories, i.e. ER, PR, Her2, etc. Maybe DHFR (dihydrofolate reductase).

Caris begins with an immunohistochemistry (IHC) analysis. IHC testing examines "dead" tissue. An IHC test measures the level of proteins in cancer cells providing clues about which therapies are likely to have clinical benefit and then what additional tests should be run. It never actually tests your tumor specimen against any drug agents.

If deemed appropriate, they will run additional tests. Fluorescent In-Situ Hybridization (FISH) is used to examine gene copy number variation in the tumor. Polymerase Chain Reaction (PCR) or DNA sequencing is used to determine gene mutations in the DNA of the tumor.

It is a tumor analysis coupled with clinical literature search, which tries to match therapies to patient-specific biomarker information to generate a treatment approach. In other words, information that may help when considering "potential" treatment options (theoretical analysis).

Rational Therapeutics uses a functional profiling platform. It takes the tumor with the surrounding tissue (intact and live) and then puts chemo on it to see which chemos (actually) kill the cancer cells.

The ability to monitor cell "function" provides clinicians with a vital method to characterize and compare activity of cells. Programmed cell death, or apoptosis, is critical in cancer formation and is often used to determine if cells are functioning properly.

Phenotype (functional profiling) analyses, measure biological signals rather than DNA indicators, provides clinically validated information and plays an important role in cancer drug selection. The data that support phenotype analyses is demonstrably greater and more compelling than any data currently generated from genotype analyses.

Funtional profiling "actually" measures the response of the tumor cells to drug exposure. Following this exposure, they measure both cell metabolism and cell morphology. 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. No matter which genes are being affected, functional profiling is measuring them through the surrogate of measuring if the cell is alive or dead.

Caris is testing for mutations, Rational Therapeutics is testing for drugs. Rating the efficacy of population research vs rating the efficacy of drugs actually tested against an individual's cancer cells.

The endpoints (point of termination) of molecular profiling (genotyping analysis) are gene expression, examining a single process (pathway) within the cell or a relatively small number of processes (pathways) to test for "theoretical" candidates for targeted therapy.

The endpoints of functional profiling (phenotyping analysis) are expression of cell-death, both tumor cell death and tumor associated endothelial (capillary) cell-death (tumor and vascular death), and examines not only for the presence of the molecular profile but also for their functionality, for their interaction with other genes, proteins and other processes occuring within the cell, and for their "actual" response to anti-cancer drugs (not theoretical susceptibility).

Again, the choice is theoretical vs actual analysis.

Sounds great except that insurance will not pay and the costs are high. Medical information like this that is so very  important should be more available to everyone. This is not just a PC issue!

On Aug 01, 2011 5:26 PM star77 wrote:

I am a patient of Dr. Nagourney at Rational Theraputics. I was diagnosed with stage 4 pancreatic cancer over a year ago. After several opinions, none to favorable, I chose Rational Theraputics because it seemed to offer the only hopeful alternative and the testing made sence. At present, My tumors are reduced to near normal and my tumor markers have been within normal rage for several months. Dr. Nagourney has been honest with me about my case and hopefully things will continue to go well in the future. I think you have to include Rational Theraputics as  one of you options.

I have my brother fighting pancreating cancer for the past 2 years. He was doing good uptill about 8 months ageo ,but now suddendly he is deteriorated.His tumor has grown and spreat to his stomach and has water. Yesterday day his Oncologist told him that they don't have any treatment .They have recommended him for trial medcine. My question to you is do you think that Rational Theraputics can still work for him . By the way he is being treated at MD Anderson ,Houston, TX., he has been using herbal medicine by DR Pankaj Naram   for pst 5 weeks but it seems it has done nothing . I hope you are doing good on your end and thanks for sharing your condition.  

Shelby

There are hundreds of different therapeutic drug regimens which any one or in combination can help cancer patients. The system is overloaded with drugs and underloaded with wisdom and expertise for using them. We are getting an expanding list of treatments which are partially effective in a minority of patients, ineffective in a majority, remarkably effective in a select few, while being enormously expensive. The fastest way to improve things and reduce cost is to match treatment to the individual cancer patient.

Going after a surgical/biopsy specimen has a role in eliminating ineffective agents and avoid unnecessary toxicity and in directing "correct" therapy. There would be a huge advantage (cost-wise) to the patient to receive a "positive/sensitive" drug, compared to a "negative/resistant" drug. The time and energy required to conduct an excisional biopsy pales in comparison to the time, energy and lost opportunities associated with months of ineffective, toxic, as well as costly therapy.

Ammarsheikh

If your brother has a viable tumor to be excised, the way labs like Rational Therapeutics and Weisenthal Cancer Group does it is they receive the ice cold tumor, straight from the patient (just as good as an ice cold kidney, straight from the patient).

They isolate 3D (three-dimensional) cell clusters, straight from the tumor, exactly as they were in the patient, add the drugs shortly after the tumor is re-warmed to body temperature, and then measure whether the drugs kill the tumor, in comparison with extensive databases of tumors with similar characteristics ("apples to apples" comparisons).

Gene tests attempt to figure out the "recipe" for your cancer. If it turns out that you have a certain mutation, statistically you may be more likely to respond to a particular treatment. But that is only based on statistics - what worked for other people with a similar cancer recipe. You want to find what works for your brother.

A functional profile assay uses a freshly biopsied piece of the tumor and throws all the various anticancer drug agents (even herbals if requested) at it to see which ones actually cause the most cancer cells to commit suicide (cell death or apoptosis). The drugs are ranked on their actual effectiveness. The most active is the drug you want to go with. It is a "real time" analysis of how your cancer cells are most likely to respond. No statistics and no guessing.

You do have to undergo a tissue biopsy in order to have a big enough sample to be tested. The reason this is important is that cancer cells don't grow in a vacuum. How they live or die has a lot to do with the chemistry and other biological functions that go on in your own body, so the cancer cells must be kept in a cluster and tested alive as if they were still inside you. You would have to arrange the biopsy through your oncologist or other doctor. The sample would then be sent to the lab for testing. It usually takes a week to get the results.

A functional profiling assay helps you and your doctor determine which anticancer drugs will most likely work best for you as an individual. The reason so many people suffer from chemotherapy is that treatment usually follows a "standard protocol" and many patients have to try 2 or 3 kinds before one works, making them sicker in the process.

Is this worthwhile? I personally feel very much so.

Greg