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caris testing

laverdiere
Posts: 9
Joined: Jan 2013

Has anyone done t he molecular testing by the company Caris, which can assist with the best chemo to use?

Tethys41's picture
Tethys41
Posts: 1057
Joined: Sep 2010

I know a number of women who have had this testing.  It is free through the Clearity Foundation.

jt25741
Posts: 23
Joined: Apr 2012

Wife had this done ---not sure if it is better or worse than those services offered by Rational Therapeutics, etc...

 

gdpawel's picture
gdpawel
Posts: 549
Joined: May 2001

Clearity Foundation is working to establish a bank of ovarian cancer samples and no one pays anything. There is no checking out of personal funds of any kind. So anyone who is having surgery and who can send a couple of blocks of frozen or fresh samples can have their costs covered by Clearity. Clearity will send the samples to Caris Diagnostics (now Miraca Life Sciences) and Clarient, Inc. for (molecular profiling) analysis.

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).

Labs like Rational Therapeutics can rely on institutions like the Vanguard Foundation to help those really in need, like the Clearity Foundation does for Caris Diagnostics.

Rational Therapeutics and Weisenthal Cancer Group both use 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.

Alexandra's picture
Alexandra
Posts: 1288
Joined: Jul 2012

I am relatively new on this site and it's the first time I read your posts. I just had to look into gdpawel's 12-year-long history on CSN.

I found your past research to be very detailed, insightful, helpful, and well-intentioned. Despite some past drama coming from the breast cancer board...

You seem to know a lot about chemo sensitivity testing and long-term dangers of Taxol.

I found your old post from 2005 (?) listing centers in US doing such testing. Are you aware of any in Ontario, Canada?

Many thanks!

 

 

 

laverdiere
Posts: 9
Joined: Jan 2013

Dear gdpawel

My husband did investigate the molecular profiling which is the only option I have since no one thought I had ovarian cancer at the time of surgery. The molecular profiling seems to be done only after the first chemo doesn't work. This is really disturbing because "the one size fits all" approach to chemo can have lasting side effects.

Has anyone had the molecular profiling for the first chemo go-around?

gdpawel's picture
gdpawel
Posts: 549
Joined: May 2001

Alexandra

Between fighting for my wife's life with this disease and researching what happened and why, I've been at this for some 17 years now. I've been interested in and studied all aspects of cell function analysis, like anyone would have an interest in molecular science or biological science.

My point with respect to cell function analysis is to educate patients and others (even doctors) that such science and technology exists, and might be very valuable. I get nothing out of my endeavors except the satisfaction of knowing that I've helped to increase the knowledge of informed consent.

In Canada, there is a typical cell-death assay based on flow cytometry, although it is not 3D (three-dimensional) analysis. If they are measuring with flow cytometry, it is with typical "single" cell culture plate plastic, the cells would attach and spread out into a 2D (two-dimensional) conformation.

Traditionally, in-vitro (in lab) cell-lines are studied in 2D monolayers, which has inherent limitations in applicability to real-life 3D in-vivo (in body) states. Cancer is already in 3D conformation. Fresh "live" cancer cells need to be profiled in 3D conformation.

Established cell-line is not reflective of the behavior of "fresh" live tumor cells in primary culture in the lab, much less in the patient. Monolayer assays performed on pre-cultured, pre-amplified tumor cells do not give clinically relevant results.

You get different results when you test passaged cell-lines compared to primary, fresh tumors. Researchers have pointed to the limitations of 2D cell-line study and chemotherapy to more correctly reflect the human body.

If you still like to look into Medicor Cancer Centres in Canada:

http://www.medicorcancer.com/chemofit4doctors.html

Laverdiere

Whether one looks into molecular profiling (theoretical genotype analysis) or upgrading the science with functional profiling (actual phenotype analysis), you should have the right chemotherapy in the first-line of treatment. There would be a huge advantage to the patient to receive a "positive/sensitive" drug, compared to a "negative/resistant" drug in the first-line setting.

Even within the cell-based assay laboratories, they vary considerably with regard to technologies, approach to testing, what they try to achieve with the testing, and cost. Some labs have been offering these assays as a non-investigational, paid service to cancer patients, in a situation where up to 30 different drugs and combinations are tested, at two drug concentrations in three different assay systems.

The problem with the "one-size-fits-all" empirical approach to chemotherapy treatment is it yields information about how large populations are likely to respond to a treatment. Doctors don't treat populations, they treat individual patients. The empirical approach doesn't tell doctors how to personalize their care to individual patients.

Patient tumors with the same histology do not necessarily respond identically to the same agent or dose schedule of multiple agents. Laboratory screening of samples from a patient's tumor can help select the appropriate treatment to administer, avoiding ineffective drugs and sparing patients the side effects normally associated with these agents. 

It can provide predictive information to help physicians choose between chemotherapy drugs, eliminate potentially ineffective drugs from treatment regimens and assist in the formulation of an optimal therapy choice for each patient (not average populations). This can spare the patient from unnecessary toxicity associated with ineffective treatment and offers a better chance of tumor response resulting in progression-free survival. 

Identifying patients with resistant neoplasms may not only spare them toxicity but may prolong their lives, by sparing them from the life shortening (mutagenic) effects of ineffective chemotherapy. 

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 empiric chemotherapy. 

With the absence of effective laboratory tests to guide physicians, many patients do not even get a second chance at treatment when their disease progresses. Spending six to eight weeks to diagnose treatment failure often consumes a substantial portion of a patient's remaining survival, not to mention toxicities and mutagenic effects.

In short, yes, patients do go for pre-testing for their first chemo go-around. In fact, more emphasis should be put on matching treatment to the individual patient, through the use of individualized pre-testing. Trying to mate a notoriously heterogeneous disease into "one-size-fits-all" treatments is disingenuous to all who are inflicted with this disease.

And the criticism remains: All of the clinical trials resources have gone toward driving a square peg (one-size-fits-all chemotherapy) into a round hole (notoriously heterogeneous disease).

In regards to your question about anyone having the molecular profiling for first chemo go-around. Someone had asked on one of the cancer boards, why it was suggested to have a molecular profiling assay AFTER chemo, which she didn't understand.

I told her that to do tumor analysis coupled with clinical trial literature search, which tries to match therapies to patient-specific biomarker information to generate a treatment approach, they do this without "actually" testing your tumor specimen against any actual drug agents. What difference does it make? They never measure any of the therapies suggested against your individual cancer cells (blind luck).

The choice is theoretical vs actual analysis. It's up to you.

Greg

laverdiere
Posts: 9
Joined: Jan 2013

Greg,

Thanks so much for your extensive knowledge. My husband and I have looked at so much information in the last 6 weeks, and unforunately the doctors did not know I had Ovarian CA when they went in to take my ovaries out. It would have been ideal to have live tissue. There is a company here in So.Cal that does the same thing as the Canadian company. So that is why I am looking at moleular profiling. The Clearity Foundation is here where I live, so will be calling them tomorrow. I have an appointment on Thursday to see the 3rd path report and decide on where to go from here. It is utterly amazing that the medical community is still not customizing care, and relaying on very toxic chemo. If I have Low Grade, not Grade 2, I am tempted to see if I have a recurrance, then do the live tissue analysis. Might give me more quality of life, more time and much less heartache. Thanks again for your information. You must be an engineer.

gdpawel's picture
gdpawel
Posts: 549
Joined: May 2001

I just wanted to point out that even some researchers in genomic medicine feel they can do better with molecular profiling if they used (at least) frozen tissue samples from a biopsy or surgical specimen. Molecular profiling can only be done "accurately" with adequate biopsy tissue. The same goes for functional profiling.

It is precisely the formalin fixed, paraffin embedded (FFPE) tissue that they feel can be done better. All samples today go into FFPE, which alters the DNA and makes gene sequencing quite compromised and difficult. One gets more "accurate" information when using intact RNA isolated from "fresh" tissue than from using degraded RNA, which is present in FFPE.

Recent papers in the journals of Nature, Science, Nature Genetics and Cell have shown that with hundreds of tumor samples full sequenced, no two cancers are the same and a lot of the action is not in the coding elements of the genes per se. They can't do it with fixed problems they are having with the way samples are handled today.

Don't forget, molecular profiling is tumor analysis coupled with clinical trial 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).

Functional profiling is tumor analysis that actually measures the response of the tumor cells to drug exposure. Following this exposure, it measures both cell metabolism and cell morphology, the integrated effect of the drugs on the whole cell, resulting in a cellular response to a drug, measuring the interaction of the entire genome (actual analysis).

Alexandra's picture
Alexandra
Posts: 1288
Joined: Jul 2012

I looked into Medicor and they require fresh tumor samples. Mine were taken out 4 months ago and saved in parafine blocks (I hope). I emailed hospital pathology dept. to try and retrieve them. Also Medicor testing is not covered by insurance. And most importantly as you have mentioned yourself there is no correlation of in vitro test results to cell behavior in the patient.  What's the point?

I like the idea of chemo sensitivity testing or functional profiling on a dead tumor cell rather than on me. I took my chances and contacted Clearity Foundation yesterday. Maybe they will accept me despite being a Canadian "outcast".

Thank you again Greg for your help and information. I had to read it like 5 times to understand. Are there any studies linking falling IQ with estrogen levels? Just kidding...Smile

gdpawel's picture
gdpawel
Posts: 549
Joined: May 2001

A number of labs work with three-dimensional (3D) tumor cell clusters. Real life 3D analysis makes it indicative of what will happen in the body. It test fresh "live" cells in their three-dimensional (3D), floating clusters (in their natural state). Even researchers at Johns Hopkins and Washington University at St. Louis found out our body is 3D, not 2D in form, undoubtedly, making this novel step better replicate that of the human body.

Other researchers have pointed to the limitations of 2D cell-line study and chemotherapy to more correctly reflect the human body. Due to their enormous potential, 3D tumor cultures are currently being exploited by many branches of biomedical science with therapeutically orientated studies becoming the major focus of research. Recent advances in 3D culture and tissue engineering techniques have enabled the development of more complex heterologous 3D tumor models.

There actually were some studies linking falling IQ with estrogen levels..... Not! LOL! I have to say that doing half the science is better than doing no science at all.

Alexandra's picture
Alexandra
Posts: 1288
Joined: Jul 2012

Yesterday I called Clearity Foundation and they said that they no longer test primary tumors, even though their web-site clearly says that they do (within 6 months of surgery).

Just after I found my tumor samples at the hospital pathology lab! I am not a happy camper.

Today someone else from there (Brenda Durand) emailed me to complete and sign all kinds of releases and consents. I spend 2 hours filling out and scanning multiple forms. 2 hours later someone else (Kathleen Zajchowski) emailed back with the same thing they told me yesterday: wait for the recurrence, then contact them. Grrr!

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