Urgent anyone know Caris Life Sciences Target Now (TN) Tumor Profiling

[sarah]

Hello All,
I'm part of a cancer support group in France and a desperate member whose wife is in danger of dying wanted to know if any of us knew this place.

Caris Life Sciences Target Now (TN) Tumor Profiling, it's in Switzerland.

I think his hope is they will find something that can be targeted with a drug. she has bc that is now is her bones and liver. she is 37 years old and had cancer for 8 years. The test is very expensive, some $6000 and of course I'm wondering is it a scam, is it totally useless?
health and happiness
love sarah

In the June 13 Time magazine (Dr. Oz is on the cover) "MD Anderson and Massachusetts General Hospitals are doing genomic analysis which uses sequencing technology to guide treatment of patients in clinical trials. Even with out the full genome map of certain cancers, clinicians are using known mutations linked to cancer to dictate which drugs patients receive. In MD Anderson's program, all lung cancer patients are offered the chance to join a trial in which their tumors are genetically analyzed for some well known genetic defects thought to play a role in cancer. About 12% of lung cancers for example, show mutations in a gene that makes a protein critical for cell growth. Patients with this aberration can enroll in trials in which FDA approved drugs targeting that mutation are being tested as a first line therapy, instead of chemotherapy, for treating their disease, giving them a head start in gaining any benefits the drugs might porvide. (At the moment, these drugs are approved only for patients with advanced cancer for whom other therapies have failed.)"

This is just a snipit of the article, I don't know anything about this, it is still something worth checking out.

Gods blessings

[Chelee]

Sarah,
I had some bone mets acting up and went for a 2nd opinion. This onc wanted to enroll me in a clinical trial so he had my iliac crest biospied and sent to Caris. I was given a copy of the "Target Now" report which was more extensive then I first thought. It had some information on it that I did not have before doing it. But I was suprised when my onc and a well known onc I showed it too both told me bascially it did nothing for them. In fact one told me it was nothing more then a very expensive report. (Here I was rather impressed with it.) So I don't know what to tell you? I have Anthem BC insurance which is a PPO so they paid for most of it. Here is a link to take you to their page if you'd like to read about it?

http://www.carislifesciences.com/oncology-target-now

This topic came up once before and another member explained in detail exactly what this Caris Target Now report is. I found it very helpful. Go to the very bottom of this link and read "gdpawel" explanation of Caris Target Now report. If you would like more information on my report feel free to ask me or send me a PM. I'll tell you exactly what's in this one.

http://her2support.org/vbulletin/showthread.php?t=50010&highlight=caris

Hope this helps some?

Chelee

[sarah]

Thanks you Chelee and unregistered for this info. It's so worrying for people in this situation as to what to try and do. and thank you for answering so quickly.
I have since learnt that his oncologist suggested doing this, not sure why or what it might show that isn't already known. It will cost him 5000 euro (about $7500) which seems hugely expensive.
health and happiness
love sarah
ps chelee, sorry to hear your hospital is not compassionate, we need that as well as good medicine when we are facing a deadly disease. They should be ashamed

[gdpawel]

In regards to the Caris Target Now, it is a tumor analysis coupled with clinical literature search, which matches therapies to patient-specific biomarker information to generate a treatment approach. Caris Target Now testing provides information that may help when considering "potential" treatment options.

Caris Target Now begins with an immunohistochemistry (IHC) analysis. 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." They never actually test your tumor specimen against any drug agents.

If there is access to a frozen sample of patient tissue available, Caris Life Sciences may also run a gene expression analysis by microarray. The microarray test looks for genes in the tumor that are associated with treatment options. IHC testing examines "dead" tissue. One gets more accurate information when using intact RNA isolated from "live" fresh tissue than from using degraded RNA, which is present in paraffin-fixed tissue.

As deemed appropriate based on each patient, Caris 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 tumor.

Caris takes the results from each test and applies the published findings from thousands of clinical trials. Based on this analysis, Caris Target Now identifies "potential" therapies for patients and their treating physicians to discuss. Again, never measuring any of the therapies against your individual cancer cells.

Caris Target Now was developed and its performance characteristics were determined by Caris Life Sciences, a medical laboratory CLIA-certified in compliance with the U.S. Clinical Laboratory Amendment Act of 1988 and all relevant U.S. state regulations. It has not been approved by the United States Food and Drug Administration. It says it right on the report.

Their molecular profiling need only obtain a small biopsy of tissue to identify the targets "most likely" to respond to available agents. However, their investigators invented a criterion of response: 1.3 fold improvement in time to progression. Patients who receive an ineffective therapy and showed disease progression, need only improve upon that short response by a mere 30% to be counted among the responders. No wonder none of the molecular assay results make sense.

A patient who fails a therapy after 10 days could theoretically be counted among the successes if their subsequent response to directed therapy was a meager 13 days in duration (J Clin Oncol 28:4877-4883. 2010). The NCI has concluded (J Natl Cancer Inst. March 16, 2010), molecular tests cannot determine treatment plans for patients. It cannot test sensitivity to any of the targeted therapies. It just tests for "theoretical" candidates for targeted therapy.

In regards to Rational Therapeutics and Weisenthal Cancer Group, both use the functional profiling platform (just call it differently), It takes the tumor with the surrounding tissue intack and then puts chemo on it to see which chemos (actually) kill the cancer cells.

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

There is much research devoted to measuring gene expression. A key challenge is differentiating changes in gene expression caused by changes in primary DNA sequence, versus those caused principally by modifications to histones and methylation of DNA.

Understanding the structural and functional relationships of cells and tissues is critical to advancements in key research disciplines, including molecular biology, genetics, reproductive function, immunology, cancer and neurobiology.

Now that the human genome has more or less been sequenced and the technologies developed to analyze numerous genes and gene products simultaneously (microarray technologies), the focus of scientific query will switch from simply identifying the gene/protein to investigating the function(s) and inter-relationships between specific gene products and specific cellular activities (drug selection).

No technology is more well suited to the investigation and simultaneous analysis of the relationships between specific target molecules, cell functions and cell sub-populations than cytometry and cytometric analysis of cell phenotype and function provides a very comprehensive overview of this ever-broadening field (function cytometric profiling).

And some inside information. Precision Therapeutics has a complement assay to their ChemoFx, which is run on a "population" of tumors. They identify the responsive, intermediately responsive, and nonresponsive patients. Then take the molecular markers and find out what these patients have in common with respect to 150 different genes.

Then they work on eliminating the genes that are irrelavent. What they get is a multi-gene predictor. It can't work without ChemoFx working. ChemoFx is the backbone of BioSpeciFx. The thing that is unique about BioSpeciFx is that the oncologist can pick and choose which markers he/she want to see. An ala carte selection if you will.

Caris' Target Now does not do this. In fact, they are running 100-120 different markers and charging for each one, with relatively no clinical relevancy to justify this.

[sarah]

thank you, I will pass this answer along as well.
nice to have somewhere to turn to.
health and happiness
sarah

[ZGatalica]

Sarah,

Comprehensive molecular tumor profiling is offered by Caris Life Sciences, founded in 2005. To date, Caris has profiled the cancers of 20,000 patients.

Caris’ evidence-based molecular profiling test, Caris Target Now, is providing some compelling success stories, which you can watch in short videos produced by the company. For the readers of this blog, the story of Melanie Smith is very compelling. Melanie was diagnosed with colorectal cancer in 2002. She had several surgeries and underwent several drug therapies, few with any success. In late 2008, Melanie’s weight was down to 75 pounds and her doctor wanted to send her home on hospice. In 2009, Melanie switched physicians. Her subsequent doctor ordered Caris Target Now testing. The testing revealed that Melanie’s cancer overexpressed HER2, as well as exhibited other promising biomarkers with known therapeutic targets that have clinical trial evidence to support their use. Melanie was given Tykerb and Herceptin and responded well. Two years later, she is doing great. See Melanie’s HER2 story.

Other patient success stories include kidney cancer patient Douglas Luckow and breast cancer patients Sandy Fehrman and Barbara Levering.

The Journal of Clinical Oncology published a pilot study about the molecular profiling performed by Caris Life Sciences in October 2010. The study looked at biomarker based therapy among a group of patients with several different cancer types—all of whom had failed more than two previous lines of chemotherapy. In 27% of the patients, the approach in this study resulted in a longer progression free survival when compared to the regimen on which the patient had just experienced progression.

The news from ASCO this year was overwhelming. A study from researchers at M.D. Anderson Cancer Center in Houston found that one in four patients who had exhausted the standard of care therapies improved after getting a drug tied to the molecular ‘glitch’ feeding their cancer (this glitch is the type of finding discovered by Caris Target Now profiling).

Molecular profiling will pave the way to understanding the way cancer is approached. It is not perfect, but companies like Caris and institutions like M.D. Anderson are constantly working to evolve the science. Because the science is relatively new, there are still pathways and biomarkers to discover, and some cancers don’t have readily identifiable targets with related drug therapies. This is where molecular profiling can fall short –when a specific patient’s cancer doesn’t have a readily identifiable target for which there is a corresponding drug to treat it.

On another note, tumor sensitivity tests (the ones that are eloquently supported by a few bloggers on HER2support.org) are different from molecular profiling. Molecular profiling is performed by running a series of tests (DNA microarray, IHC, FISH, etc) to identify information about a patient’s tumor. This information includes the expression of various biomarkers that can help guide therapy. A chemosensitivity or chemoresistance assay takes cancer cells, isolates them, incubates them with various chemotherapeutic agents, assesses cell survival and interprets the results, which are usually recorded as drug sensitive, drug resistant or intermediate. Both approaches have their supporters and their detractors. This year ASCO focused on the pathway approach to better cancer therapies and firmly pointed to molecular profiling as the future to cancer discovery going forward.

[gdpawel]

The headlong rush to develop tests to identify molecular predisposing mechansims 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.

Genetic profiles are able to help doctors determine which patients will probably develop cancer, and those who will most likely relapse. However, it cannot be suitable for specific treatments for "individual" patients. The NCI has concluded (J Natl Cancer Inst. March 16, 2010), it cannot determine treatment plans for patients. It cannot test sensitivity to any of the targeted therapies. It just tests for "theoretical" candidates for targeted therapy.

The predictions are based on the fact that a higher percentage of people with similar genetic profiles or specific mutations may tend to respond better to certain drugs. This is a refinement of statistical data, like conventional treatment is based on previous randomized clinical trials (population studies). If you are okay with that, it might be worthwhile.

Some molecular tests do utilize living cells, but generally of individual cancer cells in suspension, sometimes derived from tumors and sometimes derived from circulating tumor cells. This was tried with the human clonogenic assay, which had been discredited long ago. Again, traditionally, in-vitro (in lab) "cell-lines" have been studied in 2 dimensions (2D) which has inherent limitations iin applicability to real life 3D in-vivo (in body) states.

The October 2010 Journal of Clinical Oncology published study used immunohistochemical and microarray platforms to identify targetes for drug therapy in a population of previously treated patients. Patients eligible had to have clear disease progression on prior therapy and received at least two prior lines of systemic chemotherapy.

“Success” was defined as a time to progression (TTP) of at least 30% longer than the TTP of the most immediate prior therapy. A total of 18 patients (of 66) achieved this 30% improvement in time to progression. The algorithm compared each patient's last TTP as the denominator and their targeted TTP as the numerator to idenfity a 1.3 fold improvement.

The null hypothesis was 15% or less of the sample would achieve this 1.3 fold improvement with a 90% power, P = .05. Drug selection was hierarchical, with gene array + IHC, followed by IHC alone, followed by gene array alone, with pts failing to provide a result offered physicians choice.

Only 62% of all the accrued patients were treated. The drop out of 40 patients may have served to cull the most vigorous from the herd, introducing a bias for survival regardless of intervention.

The functional profiling platform 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.

Cancer is already in 3D conformation. Cell-based functional profiling cultures "fresh" live tumor cells in 3D conformation and profiles the function of cancer cells (is the whole cell being killed regardless of the targeted mechanism or pathway). It distinguishes between susceptibility of cancer cells to different drugs in the same class and the susceptibility to combinations. In other words, which combinations are best and in what sequence would they be most effective.

The key to understanding the genome is understanding how cells work. The ultimate driver is a functional profiling (is the cell being killed regardless of the mechanism) as opposed to a molecular profile (does the cell express a particular target that the drug is supposed to be attacking). While a molecular profile tells you whether or not to give "one" drug, a functional profile can find other compounds and combinations and can recommend them from the one assay.

The core of the functional assay 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 therapeutic targets, but these targets require the determination of cellular endpoints.

Cell-based functional assays are 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 assay.

[sarah]

Hello Gdpawel,
Thank you for this informative answer. If I understand it correctly, it is less helpful for individuals and more helpful for statistics.
Health and happiness
Sarah

[gdpawel]

Sarah

That is a very good way to put it! Human beings are demonstrably more than the sum of their genes. Cancer biology and the study of cancer therapy are many things, but simple is not one of them. Complex problems require solutions that incorporate all of their complexities, however uncomfortable this may be for genomic investigators.

Greg