Has anyone had a blueprint of their tumor done?

• By momanderson920
• Posted October 10, 2009 at 8:20 am
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Thanks for sharing this. I will most definitely look into it! I had read that this cancer is not one type but many which makes it unique in treatment.

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• By Jennali
• Posted October 10, 2009 at 6:32 pm
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This looks extremely interesting. I am going to get the info to my gyn/onc somehow. I have to find out if it is possible to obtain an archived tumor sample.

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• By gpawelski
• Posted October 10, 2009 at 9:49 pm
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In chemotherapy selection, molecular profiling 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.

Functional profiling examines not only for the presence of the molecular profile but also for their functionality, for their interaction with other genes, proteins, and processes occurring within the cell, and for their response to anti-cancer drugs.

The goal of molecular testing is to look for patterns of normal and abnormal gene expression which could suggest that certain proteins might or might not be produced within a cell. However, just because a gene is present, it does not mean that an associated protein has been produced.

Protein testing goes one step further by testing to see if the relevant protein actually has been produced. However, even Protein testing cannot tell us if a protein is functional or how it will interact with other proteins in the presence of anti-cancer drugs.

Gene and protein testing involve the use of dead, formaldehyde preserved cells that are never exposed to chemotherapy drugs. Gene and protein tests cannot tells us anything about uptake of a certain drug into the cell or if the drug will be excluded before it can act or what changes will take place within the cell if the drug successfully enters the cell.

Gene and protein tests cannot discriminate among the activities of different drugs within the same class. Instead, gene and protein tests assume that all drugs within a class will produce precisely the same effect, even though from clinical experience, this is not the case. Nor can gene and protein tests tell us anything about drug combinations.

Functional tumor cell profiling tests living cancer cells. It assesses the net result of all cellular processes, including interactions, occurring in real time when cancer cells actually are exposed to specific anti-cancer drugs. It can discriminate differing anti-tumor effects of different drugs within the same class. It can also identify synergies in drug combinations.

Gene and protein tests are better suited for ruling out "inactive" drugs than for identifying "active" drugs. When considering a cancer drug which is believed to act only upon cancer cells that have a specific genetic defect, it is useful to know if a patient's cancer cells do or do not have precisely that defect.

Although presence of a targeted defect does not necessarily mean that a drug will be effective, absence of the targeted defect may rule out use of the drug. Of course, this assumes that the mechanism of drug activity is known beyond any doubt, which is not always the case.

Although gene and protein testing currently are limited in their reliability as clinical tools, the tests can be important in research settings such as in helping to identify rational targets for development of new anti-cancer drugs.

As you can see, just selecting the right test to perform in the right situation is a very important step on the road to personalizing cancer therapy.

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• By Jennali
• Posted October 10, 2009 at 10:01 pm
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Okay...so bottom line, this test is of limited value for those of us in treatment? It is more useful as a research tool? Sorry...I am not completely sure of your conclusion.

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• By gpawelski
• Posted October 10, 2009 at 11:42 pm
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Jennali

In this particular case, a molecular profile may help match a patient with an appropriate clinical trial. It can be important in research settings such as in helping to identify rational targets for development of new anti-cancer drugs.

It would be beneficial to find panels of markers that can predict the likelihood of cancer recurrence in various populations. By testing the gene expression markers of a patient, oncologists can identify those patients unlikely to benefit from adjuvant chemotherapy from those that would.

You may identify gene expression patterns which correlate with chemo sensitivity. But it can be hard and even impossible to tell what exactly you are measuring: is it intrinsic aggressiveness of the tumor? Sensitivity to this particular drug? Sensitivity to that particular drug? You find a gene expression panel which correlates with something, but picking apart the pieces is hard.

Sure, we know that ER predicts for hormone response, Her2/neu gene amplification predicts for response to Herceptin, and certain mutations predict for response to Iressa and Tarceva, but that is far from proving that profiling gene mutations will work in a more general setting.

Some researchers have put enormous efforts into genetic profiling as a way of predicting patient response (clinical responders) to various therapies. However, none of the genetic tests can predict clinical responders. Molecular predisposing mechanisms do not guarantee that a drug (or combination of drugs) will be effective for an individual patient. Drugs can work in ways that we don't suspect. A more suitable platform can be used to utilize cell-based functional profiling tests to better select a repertoire of available drugs to improve the efficacy of chemotherapy.

A challenge facing pharmacogenetics is the number and complexity of interactions a drug has with biological molecules in the body. Variations in many different molecules may influence how someone responds to a medicine. Teasing out the genetic patterns associated with particular drug responses could involve some intricate and time-consuming scientific detective work.

Several new targeted drugs have been introduced during the last few years. Most of them have been developed for use in solid tumors but some have also emerged for hematological maligancies. These new targeted drugs mostly need to be combined with active chemotherapy to provide any benefit and the need for predictive tests for individualized therapy selection has increased.

Unfortunately, the introduction of these new drugs has not been accompanied by specific predictive tests allowing for a rational and economical use of the drugs. Drugmakers have said that pharmacogenetics will not change the landscape for the bulk of pharmaceuticals for several years. Pharmacogenetics is not going to transform the market any time soon.

There are a number of laboratory tests that are better able to predict the ability of targeted drugs, to produce positive clinical responders (outcomes). Given the technical and conceptual advantages of oncologic in vitro chemoresponse assays, together with their performance and the modest efficacy of therapy prediction based on analysis of genome expression, there is reason for a renewal in the interest for these tests for optimized use of medical treatment of malignant disease.

You could begin to do this if you combine gene expression studies with cell culture studies. Use the cell culture to define the difference between sensitivity and resistance. Then see which pattern correlates with which for individual tumors and individual drugs.

Then you come to the 1,000 pound gorilla of a question: What effect will the different individual drugs have in combination in different, individual tumors? This is where functional profiling will be able to provide uniquely valuable information. But it's not one versus the other. The best thing is to combine these different tests in ways which make the most sense. We cannot afford too much trial and error treatment.

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• By Luann
• Posted October 11, 2009 at 8:10 am
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I just recently sent in information to The Clearity Foundation and am waiting to hear from them.
Any information gained from blue printing tumor blocks will be put into a data base with informed consent from the patient and could help further
OVCA research. The foundation also provides genetic testing, something I could not afford as
my insurance would not pay for it.
KUDOS to Dr. Shawver of The Clearity Foundation for her efforts....she is an ovarian cancer survivor.
If this is one way that I can help further research for
this disease, I am happy to do it.
If this information will help provide information for
better treatments for others as well as for me in case of recurrence, once again, I feel that it is worth the effort I put into helping The Clearity Foundation gather information.
For those of you who have an interest in this, contact
The Clearity Foundation. They will send you the necessary paper work that needs to be filled out and signed and they will take it from there.

Blessings!
Luann

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• By Ovacom06
• Posted October 11, 2009 at 11:34 am
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Luann I agree with you. I may not benefit from this since I have already gone through treatment. But I am willing to do just about anything in the name of research to help others. I have already sent off for information also.

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• By gpawelski
• Posted November 5, 2009 at 6:22 pm
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Functional profiling with cell culture assays that predicts for patient survival in ovarian cancer

There is Functional Profiling that shows data indicating a near doubling in the survival of patients with platinum-resistant ovarian cancer, striking correlations between platinum activity and patient survival in previously-untreated ovarian cancer, and a comprehensive meta-analysis of scores of studies reporting response and survival correlations in thousands of patients.

With relapsed, platinum-resistant ovarian cancer, every clinical trial in history has just shown a 10-12 month median survival in this setting. However, background data (680 fresh surgical specimens) for the design of a cliinical trial to determine the efficacy of assay-directed therapy of platinum-resistant ovarian cancer, submitted to the 2003 Society of Gynecologic Oncology meeting, had a 27 month median survival and a fair number of long-term survivors. All specimens were tested with two separate Medicare-approved cell culture assays (DISC and MTT) having cell-death endpoints.

Cell culture drug resistance testing in platinum-resistant ovarian cancer
Sub-category: Translational research
Category: Ovarian
Control/Tracking Number: 2004-AB-171-SGO
Activity: Abstract Richard H. Nalick, Hospital of the Good Samaritan, Los Angeles, CA; Larry M. Weisenthal, Weisenthal Cancer Group, Huntington Beach, CA

Objectives: Obtained background data required for the design of a clinical trial to determine the efficacy of assay-directed therapy of platinum-resistant ovarian cancer.

Methods: 680 fresh surgical specimens of ovarian cancer were submitted from outside hospitals for the purpose of obtaining cell culture assay data to assist in the choice of chemotherapy on a non-investigational basis. Virtually all surgical specimens were tested with two separate Medicare-approved cell culture assays (DISC and MTT) having cell-death endpoints.

Results: Validation of cell culture assays for identifying platinum resistance was as follows.

1. Surgical specimens from platinum-treated patients had significantly greater in vitro resistance to platinum than surgical specimens from untreated patients.
2. Untreated patients without in vitro resistance to platinum had significantly better long-term, overall survival than patients with in vitro resistance to platinum (2775 vs 713 days, P2=0.0066).
3. Surgical specimens obtained within 6 months of platinum-based therapy had significantly greater in vitro resistance to platinum than surgical specimens obtained more than 6 months after the last platinum-based therapy.
4. In patients more than 6 months after the last platinum-based therapy, in vitro resistance to platinum predicted for significantly inferior long-term, overall survival (950 days vs median not reached, P2<0.05).

Comparing early relapse surgical specimens with untreated surgical specimens, the following regimens showed significantly inferior activity in early relapse surgical specimens: cisplatin, carboplatin, oxaliplatin, melphalan, thiotepa, mitomycin, paclitaxel, and the topotecan + cicplatin combination. The following did not show significantly inferior activity in ER surgical specimens: gemcitabine, etoposide, vinorelbine, fluorouracil, epirubicin, pegylated doxorubicin, topotecan, irinotecan, docetaxel, and all 3 gemcitabine + platinum combinations. Although the gemcitabine + platinum combination was the only active regimen in 25% of the early relapse surgical specimens, in 30% there was at least one active single agent, and in another 20%, other drug combinations were superior to gemcitabine + platinum, some of these being irinotecan + mitomycin, paclitaxel + cyclophosphamide, cyclophosphamide + etoposide, platinum + topotecan, and gemcitabine + melphalan. With a minimum follow-up of 3 years post-assay, early relapse (primary refractory and first relapse) patients had a median long-term, overall survival of 849 days, while all early relapse patients (including multiple relapse) had a median survival of 612 days. All late relapse patients had a median long-term, overall survival of 1244 days.

Conclusions: These results support a 3-armed, prospective randomized trial in early relapse patients to compare physician's choice chemotherapy, assay-directed therapy, and the 3 gemcitabine + platinum combination.

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