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Both Jean Mckibben and Debbie Bozsa post on ACOR (Mailing List - Ovarian Cancer) about
molecular profiling at The Clearity Foundation and their
website:www.clearityfoundation.org multiple times this year.
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"I had my 4th debulking surgery on 3/3/11 for
my 5th recurrence. Initially, I did not think about to do molecular
profiling because I thought it will need a lot paper work, energy and money to
do it. When you go through lot of treatments for ovarian cancer, you feel
that every minute counts down your life, and you just want to spend time and
money for something enjoyable. Jean encouraged me to do the molecular profiling
when we exchanged email privately. I sent in my request for the test on
3/16/11, and I got my partial result in a month, and the final result on
5/16/11. I highly recommend the test. After my surgery, my chemotherapy choice
was Doxil or Topotecan. I tried Doxil first, and then molecular profiling
showed I am benefit from Doxil, not benefit from Topotecan. Now my doctor
treats me with the confidence based on those biomarkers. My CA125 has been
going down with 2 treatments although I have skin rash and lesions due to the
side effects of Doxil.
When you go to Clearity Foundation web site, there are 3
parts.
1. Caris Life Science: They do Target Now biomarkers for
drugs including: paclitaxel/docetaxel, cisplatin/carboplatin, trastuzumab,
letrozole, tamoxifen, doxorubicin, topotecan/irinotecan and temozolomide. They
will tell you from which drug you may benefit, which not, based on your biomarkers. There
is an 11 page report sent to your doctor, including biomarker description and
reference. They send the bill to insurances and patients.
2. Clarient, Inc:
They do more tests for biomarkers to compare your biomarkers to other ovarian
cancer patients in their Diane Barton Database. Dr. Laura Shawver, the founder
of The Clearity Foundation, will email the result to you and call you to
explain the result, and may suggest some new target therapy or clinical trials.
The Clarient test will be paid by Clearity Foundation.
3. The Clearity Foundation:
They help people to pay the test cost if patients have no insurance or their
insurances do not pay for the test. They have a one page grant application
for patients to complete, and can approve the application by email in one
day. People working at The Clearity Foundation are very friendly and
helpful. Please call 1-855-856-0654 if you have any question.
Please know that molecular profiling is different from
tumor sensitivity or resistant assay. Tumor sensitivity or resistant
assay uses fresh tissue to culture tumor cells, add different chemo drugs, and
then sees which chemo drug kills them (cancer cells). When I had my 3th
debulking surgery for my 4th recurrence one year ago, my doctor sent
for a tumor resistant assay. However, I did not get any result from the test because
my tumor cells did not grow in their cell culture. The molecular profiling test
uses tumor samples from biopsy or surgery in paraffin sections. The samples do
not need to be fresh, can be a few years old. They do special staining to find
biomarkers."
Yi
Yes, "molecular profiling" is very different from a tumor sensitivity assay (functional profiling). Whenever you test tumor samples from biopsy or surgery in paraffin sections, you get different results when you test passaged cells (cell-line in paraffin) compared to primary, fresh "live" tumor cells. What works in cell-lines does not often translate into human beings.
ReplyDeleteAs a general rule, studies from cell-lines, tumor cells are cultured and manipulated so that they continue to divide. The problem is that cell-lines do not predict for disease or patient specific drug effects. If you can kill ovarian cancer cell-lines with a given drug, it doesn't tell you anything about how the drug will work in real world, clinical ovarian cancer (real-world conditions).
There are conceptual weaknesses of 2D (monolayer) vs 3D (conformation). When amplifying cells outside of the body, this results in a subpopulation selection, when cells are actually passaged (grown to confluence, split/diluted and re-plated, grown again to confluence and again split, etc.).
Research on cancer progression has been drawn largely using models that grow cancer cells in plastic dishes (hence the term grown in petri dishes). Research reveals a major shortcoming in the experimental systems used to study cancer development.
When using simplified culture systems in which cells are grown on plastic, cancer cells grow as a 2D monolayer and lack the three-dimensional (3D) tissue structure seen in human cancer. As a result, complex interactions that occur between the cancer cells and the surrounding tissue layers are not accounted for.
In a tumor sensitivity assay (functional profiling), there is no "growing" of cells as in the old cell-growth assays (resistance assay). Cells are taken fresh "live" in their three dimensional, floating clusters, cultured in conical polypropylene microwells for 96 hours to increase the proportion of tumor cells, relative to normal cells.
When allowed to grow in vitro, "living" cancer cells develop into these tiny microspheroid clusters that form a complex biosystem in which each malignant cell reacts upon its fellow colonists in subtle but important ways.
Analysis of microspheroids (microclusters) with "cell-death" assays, provides a snapshot of cancer's behavior within the human body and provides a more accurate representation of how cancer cells are likely to respond to treatment in the clinic. There is no manipulation of isolated cancer cells to make them grow, which was an important point of distinction with earlier cell-growth assays.
They distinguish between a disease phenotype (what an organism will finally display) from what may be numerous genotypes (sequence of DNA an organism possesses). The diagnostic product uses tissue obtained from biopsy or surgery, and cultured to maintain as faithfully as possible the cancer cell's native "niche" and physiologic state within the tumor.
The cell "function" method is not hampered by the problems associated with gene expression tests (molecular profiling). 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.