Advice pls : Fresh tumor sample what to do with it?

[fullofbeans]

Hi All,

Since I should have another resection of lung tumors in about 3 weeks, i wonder if you know of a place where I could have as many receptors identified as possible?

I remember Lani mentioning a research place.

I know that samples can be kept cold and sent within 24h to any major cities in the world.

[Becky]

There is a place. Give me a day or two and I will come up with it. Sending frozen or fresh samples is possible to any major cancer center such as Sloan Kettering, etc. I did that with mine to get a second pathology opinion.

However, they just do the usual - ER, PR, Her2, grade, clean margins. I suspect you want more such as Her1 (aka EGFR) as well as if it is PTEN positive and TOP2A positive. Is that right? There is a lab that I looked into but don't have the name at my fingertips but I will get it unless Lani responds and knows.

[fullofbeans]

Yes indeed Becky I wanted more than the usual her2/pr/er.. if that is possible..

[ElaineM]

You might be interested in some chemo sensitivity testing after you do the other lab work. You can do a search on the internet for chemo sensitivity testing and bring the search results to your doctor for discussion.
In chemo sensitivity testing the lab matches pieces of your tissue with different kinds of chemo and/or targeted drugs to see which drugs kill more cancer.
The results might be helpful in deciding which drugs to take.
Good luck.

[Rich66]

http://her2support.org/vbulletin/sho...355#post222355

[gdpawel]

There is molecular profiling and there is functional profiling. The former testing is theoretical and the latter is actual.

In drug selection, molecular (genetic) testing examines a single process within the cell or a relatively small number of processes. The aim is to tell if there is a theoretical predisposition to drug response. It attempts to link surrogate gene expression to a theoretical potential for drug activity. Patients' cancer cells are never exposed to chemotherapy drugs. It relies upon a handful of gene patterns which are thought to imply a potential for drug susceptibility. In other words, molecular testing tells us whether or not the cancer cells are potentially susceptible to a mechanism/pathway of attack. It doesn't tell you if one drug is better or worse than another drug which may target a certain mechanism/pathway.

Functional profiling doesn't dismiss DNA testing, it uses all the information, both genomic and functional, to design the best treatment for each individual, not populations. Laboratories like Rational Therapeutics and Weisenthal Cancer Group test for a lot more than just a few mutations. The cell is a system, an integrated, interacting network of genes, proteins and other cellular constituents that produce functions. One needs to analyze the systems' response to drug treatments, not just a few targets (pathways).

Their functional profiling test assesses the activity of a drug upon combined effect of all cellular processes, using several metabolic (cell metabolism) and morphologic (structure) endpoints, at the cell "population" level, rather than at the "single cell" level, measuring the interaction of the entire genome.

Examining a patient's DNA can give physicians a lot of information, but as 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, just "theoretical" candidates for targeted therapy.

Just recently, an International consortium of cell biologists decided to name it Personalized Cancer Cytometric testing, after the first head-to head clinical trial comparing molecular gene testing vs personalized cancer cytometrics.

http://cancerfocus.org/forum/showthread.php?t=3474

[fullofbeans]

Thank you for all the advice above I am still studying them and will let you know what I will try. thanks a lot.
FOB

[Joan M]

Here's an article that appeared in the NYT in the summer about chemo sensitivity testing:

How Bright Promise in Cancer Testing Fell Apart
By GINA KOLATA
Published: July 7, 2011

When Juliet Jacobs found out she had lung cancer, she was terrified, but realized that her hope lay in getting the best treatment medicine could offer. So she got a second opinion, then a third. In February of 2010, she ended up at Duke University, where she entered a research study whose promise seemed stunning.

Doctors would assess her tumor cells, looking for gene patterns that would determine which drugs would best attack her particular cancer. She would not waste precious time with ineffective drugs or trial-and-error treatment. The Duke program — considered a breakthrough at the time — was the first fruit of the new genomics, a way of letting a cancer cell’s own genes reveal the cancer’s weaknesses.

But the research at Duke turned out to be wrong. Its gene-based tests proved worthless, and the research behind them was discredited. Ms. Jacobs died a few months after treatment, and her husband and other patients’ relatives have retained lawyers.

The episode is a stark illustration of serious problems in a field in which the medical community has placed great hope: using patterns from large groups of genes or other molecules to improve the detection and treatment of cancer. Companies have been formed and products have been introduced that claim to use genetics in this way, but assertions have turned out to be unfounded. While researchers agree there is great promise in this science, it has yet to yield many reliable methods for diagnosing cancer or identifying the best treatment.

Instead, as patients and their doctors try to make critical decisions about serious illnesses, they may be getting worthless information that is based on bad science. The scientific world is concerned enough that two prominent groups, the National Cancer Institute and the Institute of Medicine, have begun examining the Duke case; they hope to find new ways to evaluate claims based on emerging and complex analyses of patterns of genes and other molecules.

So far, the Food and Drug Administration “has generally not enforced” its regulation of tests created by individual labs because, until recently, such tests were relatively simple and relied heavily on the expertise of a particular doctor, said Erica Jefferson, a spokeswoman for the agency. But now, with labs offering more complex tests on a large scale, the F.D.A. is taking a new look at enforcement.

Dr. Scott Ramsey, director of cancer outcomes research at the Fred Hutchinson Cancer Center in Seattle, says there is already “a mini-gold rush” of companies trying to market tests based on the new techniques, at a time when good science has not caught up with the financial push. “That’s the scariest part of all,” Dr. Ramsey said.

Doctors say the heart of the problem is the intricacy of the analyses in this emerging field and the difficulty in finding errors. Even well-respected scientists often “oversee a machine they do not understand and cannot supervise directly” because each segment of the research requires different areas of expertise, said Dr. Lajos Pusztai, a breast cancer researcher at M. D. Anderson Cancer Center at the University of Texas. As a senior scientist, he added, “It’s true for me, too.”

The Duke case came right after two other claims that gave medical researchers pause. Like the Duke case, they used complex analyses to detect patterns of genes or cell proteins. But these were tests that were supposed to find ovarian cancer in patients’ blood. One, OvaSure, was developed by a Yale scientist, Dr. Gil G. Mor, licensed by the university and sold to patients before it was found to be useless.

The other, OvaCheck, was developed by a company, Correlogic, with contributions from scientists from the National Cancer Institute and the Food and Drug Administration. Major commercial labs licensed it and were about to start using it before two statisticians from M. D. Anderson discovered and publicized its faults.

The Duke saga began when a prestigious journal, Nature Medicine, published a paper on Nov. 6, 2006, by Dr. Anil Potti, a cancer researcher at Duke University Medical Center; Joseph R. Nevins, a senior scientist there; and their colleagues. They wrote about genomic tests they developed that looked at the molecular traits of a cancerous tumor and figured out which chemotherapy would work best.

Other groups of cancer researchers had been trying to do the same thing.

“Our group was despondent to get beaten out,” said Dr. John Minna, a lung cancer researcher at the University of Texas Southwestern Medical Center. But Dr. Minna rallied; at the very least, he thought, he would make use of this incredible discovery to select drugs for lung cancer patients.

First, though, he asked two statisticians at M. D. Anderson, Keith Baggerly and Kevin Coombes, to check the work. Several other doctors approached them with the same request.

Dr. Baggerly and Dr. Coombes found errors almost immediately. Some seemed careless — moving a row or a column over by one in a giant spreadsheet — while others seemed inexplicable. The Duke team shrugged them off as “clerical errors.”

And the Duke researchers continued to publish papers on their genomic signatures in prestigious journals. Meanwhile, they started three trials using the work to decide which drugs to give patients.

Dr. Baggerly and Dr. Coombes tried to sound an alarm. They got the attention of the National Cancer Institute, whose own investigators wanted to use the Duke system in a clinical trial but were dissuaded by the criticisms. Finally, they published their analysis in The Annals of Applied Statistics, a journal that medical scientists rarely read.

The situation finally grabbed the cancer world’s attention last July, not because of the efforts of Dr. Baggerly and Dr. Coombes, but because a trade publication, The Cancer Letter, reported that the lead researcher, Dr. Potti, had falsified parts of his résumé. He claimed, among other things, that he had been a Rhodes scholar.

“It took that to make people sit up and take notice,” said Dr. Steven Goodman, professor of oncology, pediatrics, epidemiology and biostatistics at Johns Hopkins University.

In the end, four gene signature papers were retracted. Duke shut down three trials using the results. Dr. Potti resigned from Duke. He declined to be interviewed for this article. His collaborator and mentor, Dr. Nevins, no longer directs one of Duke’s genomics centers.

The cancer world is reeling.

The Duke researchers had even set up a company — now disbanded — and planned to sell their test to determine cancer treatments. Duke cancer patients and their families, including Mrs. Jacobs’s husband, Walter Jacobs, say they feel angry and betrayed. And medical researchers see the story as a call to action. With such huge data sets and complicated analyses, researchers can no longer trust their hunches that a result does — or does not — make sense.

“Our intuition is pretty darn poor,” Dr. Baggerly said.

This article has been revised to reflect the following correction:

Correction: July 7, 2011


An earlier version of this article misstated Dr. Steven Goodman's affiliation at Johns Hopkins University. He is a professor of oncology, pediatrics, epidemiology and biostatistics, not the director of oncology biostatistics.

This article has been revised to reflect the following correction:

Correction: July 16, 2011

Joan

[gdpawel]

This was not about "chemo sensitivity testing." This was about microarrays and the whole concept of using molecular signatures of any kind to do anything beyond the most straightforward of cases (i.e. single gene mutations, etc).

Here we thought that we'd at least be selecting single agents on the basis of molecular technologies. But the investigator who seemingly made the most progress in this - Anil Potti, the pioneer of personalized medicine using gene signatures to predict responses to chemotherapy - had been discredited.

Dr. Robert Nagourney, one of the pioneers of cell culture assays (chemo sensitivity testing), has often described his personal misgivings surrounding the application of gene profiles for the prediction of response to therapeutics. His initial concerns regarded the oversimplification of biological processes and the attempt of analyte-driven investigators to ascribe linear pathways to non-linear events.

The complexities of human tumor biology took a turn toward the incomprehensible with the publication of a lead article in Nature by the group from Harvard under Dr. Pier Paulo Pandolfi. Dr. Nagourney sat in as Dr. Pandolfi reviewed his work during the Pezcoler Award lecture, held Monday, April 4, 2011, in Orlando at the AACR meeting.

What Dr. Pandolfi’s group found was that gene regulation is under the control of messenger RNA (mRNA) that are made both by coding regions and non-coding regions of the DNA. By competing for small interfering RNAs (siRNA) the gene and pseudogene mRNAs regulate one another. That is to say that RNA speaks to RNA and determines what genes will be expressed.

To put this in context, Dr. Pandolfi’s findings suggest that the 2 percent of the human genome that codes for known proteins (the part that everyone currently studies) represents only 1/20 of the whole story. One of the most important cancer related genes (PTEN), is under the regulation of 250 separate, unrelated genes. Thus, PTEN, KRAS and all genes, are under the direct regulation and control of genetic elements that no one has ever studied.

This observation represents one more nail in the coffin of unidimensional thinkers who have attempted to draw straight lines from genes to functions. This further suggests that attempts on the part of gene profilers to characterize patients likelihoods of response based on gene mutations are not only misguided but, may actually be dishonest.

The need for phenotype analyses like the functional profiling performed at Rational Therapeutics (or Weisenthal Cancer Group) has never been greater. As the systems biologists point out, complexity is the hallmark of biological existence. Attempts to oversimplify phenomena that cannot be simplified, have, and will continue to, lead us in the wrong direction.

Literature Citation: Poliseno, L., et al. 2010. A coding-independent function of gene and pseudogene mRNAs regulates tumor biology. Nature. 2010 Jun 24; 465(7301):1016-7.)

[DeenaH]

Thank you for posting that Greg!! I had my chemo sensitivity testing with RT and Dr. Nagourney. I have already had a great response to my first line since the assay. I am on my second now. After this, we are looking at clinical trials, but I am avoiding such toxic treatments as Carbo/Gemzar because I know they will not work. If you are already having the tissue removed, it is a no brainer IMO to send it to RT for the assay. You will be in the best position possible with that invaluable information. The tissue must be live, and they need at least 1cm. Good luck!
Deena

[gdpawel]

Deena

While cell function analysis has found the clinical responses to combination of Gemzar + Platinum unprecedented, those responses are not 100%. Other examples of alkylating platinum compounds are Chlorambucil (Leukeran) and Melphalan (Alkeran). Finding what "targeted" therapies would work for what cancers is very difficult. A lot of trial-and-error goes along trying to find out. And they have their share of toxicity also.

Perhaps a clinical trial will be effective for you. Best of luck!

Greg

[Becky]

http://investing.businessweek.com/re...vcapId=9570759

http://www.yellowpages.com/westmont-il/mip/targeted-molecular-diagnostics-5204372



Here is the place that will do extensive marker testing.