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Molecular profiling reveals differences between primary and recurrent ovarian cancers

Tethys41's picture
Tethys41
Posts: 1053
Joined: Sep 2010

http://medicalxpress.com/news/2012-02-molecular-profiling-reveals-differences-primary.html

carolenk's picture
carolenk
Posts: 909
Joined: Feb 2011

I found an interesting article on the same web site as above about the value of taking anti-platelet therapy to increase survival after ovarian cancer.

http://m.medicalxpress.com/ovariancancer-cancer-cancerpatients_news248544367.html

Tethys41's picture
Tethys41
Posts: 1053
Joined: Sep 2010

So maybe all those treatments that cause the platelets to tank are helping in other ways.

whiterose
Posts: 89
Joined: Jan 2012

I knew this topic rang a bell.....I had an article archived about high platelet counts:

http://m.medicalxpress.com/news/2012-02-high-platelets-ovarian-cancer-patients.html

anicca's picture
anicca
Posts: 324
Joined: Dec 2010

Thank you, this is very interesting. No one knows why OVC can recur after many years, but studies comparing molecular profiles of original tumors to those of early recurrences vs comparisons of profiles of original tumors to those of late onset recurrences might shed some light. I hope someone is doing this!

whiterose
Posts: 89
Joined: Jan 2012

Tethys, I noticed that the research paper was provided by The Clearity Foundation. I've heard of this org. before, was wondering if anyone else had any knowledge? Supposedly they test you individually to see which treatments are best for you, as well as recommend clinical trials that would be best for you.....Would appreciate any info., especially comments from someone who has gone through this process.....

kayandok
Posts: 1223
Joined: Jun 2008

I have had the Clearity Foundation profiling done and several chemo essays. My doctor does look at this info, when he decides on my treatment after chemo.The Clearity Foundation does a lot of tests on things that haven't all been approved, but will help you with finding a trial to participate in if your tumor shows a good result. I had a profile done in 2008. I have also had chemo essays done after surgery, to help decide which one would be the best. Cancer mutates, so what works initially, doesn't necessarily work later.

I attibute my 5 year survival to surgery and help from all the testing, I recommend it. I am fortunate that my doctor does look at this stuff, although it is controversial and not 100%.

whiterose
Posts: 89
Joined: Jan 2012

Thank you kayandok, your information was very helpful. I couldn't tell if the organization was legit. or not.

gdpawel's picture
gdpawel
Posts: 545
Joined: May 2001

The Clearity Foundation has developed a process for generating this personalized diagnostic information using commercially-available molecular profiling technologies and then analyzing the results using its Diane Barton Database.

However, all DNA or RNA-type tests are based on population research (not individuals). They base their predictions 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.

It is currently not routine practice to re-biopsy metastatic tissue to re-evaluate treatment options based on tumor characteristics. This is despite the fact that, upon progression to metastasis, cancers can evolve, resulting in changes in mutations and expression levels of specific biomarkers. Biological changes between the primary and secondary tumors can occur, but have not been systematically studied.

This has been published in 1983, 1984, 1986 by cell function analysis. It's called acquired drug resistance -- ovarian cancer clearly changes over time (Weisenthal, L.M. et al. Cancer Res 43:749-57,'83 - Recent Results Cancer Res 94:161-73,'84 - Cancer Treat Rep 70:1283-95,'86)

Improving and optimizing the care of patients with recurrent ovarian cancer relies on a thorough understanding of the biology of the disease and how it may differ between the primary and the metastatic disease setting. The major reasons that biopsies are not part of standard care are the lack of previous evidence of utility, reluctance of allowing an invasive, surgical procedure for an advanced-disease patient, and potential harm of a false-negative result. However, when safe and relatively easy to carry out, a biopsy of metastatic disease has the potential to impact treatment of choice.

Previous studies have found various degrees of heterogeneity observed when they compared these primary lesions with the metastatic sites of spread. The investigators inferred a branched evolution where tumors evolved into clones, some spreading to distant sites, while others manifested different features within the primary tumor themselves. Interestingly, when primary sites were matched with metastases that arose from that site, there was greater consanguinity between the primary and met than between one primary site and another primary site in the same kidney. Another way of looking at this is that your grandchildren look more like you, than your neighbor.

This study is another recent example of a growing litany of observations that call into question molecular biologist’s preternatural fixation on genomic analyses. Human biology is not simple and malignantly transformed cells more complex still. Investigators who insist upon using genomic platforms to force disorderly cells into artificially ordered sub-categories, have once again been forced to admit that these oversimplifications fail to provide the needed insights for the advancement of cancer therapeutics. Those laboratories and corporations that offer “high price” genomic analyses for the selection of chemotherapy drugs should read this study and related articles carefully as these reports portend a troubling future for their current business model.

The tumor of origin and the associated mets tend to retain consanguinity. That is, the carcinogenic processes that underlie the two populations are related. This is the reason they do not see "mixed responses" (one place in the body getting better and another place in the body getting worse), but instead, generally see response or non-responses.

Heterogeneity likely underlies the recurrences that are seen in almost all patients. This is why they try to re-biopsy and re-evaluate when recurrences are observed. Heterogeneity remains a theoretical issue no matter what platform one uses. Why complicate this fact by using a less biologically relevant method like genomics that only scratches the surface of the tumor biology?

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.

Contrary to analyte-based genomic and proteomic methodologies that yield static measures of gene or protein expression, functional profiling provides a window on the complexity of cellular biology in real-time, gauging tumor cell response to chemotherapies in a laboratory platform.

By examining drug induced cell death, functional analyses measure the cumulative result of all of a cell's mechanisms of resistance and response acting in concert. Thus, functional profiling most closely approximates the cancer phenotype.

Insights gained can determine which drugs, signal transduction inhibitors, or growth factor inhibitors induce programmed cell death in individual patients' tumors. Functional profiling is the most clinically validated technique available today to predict patient response to drugs and targeted agents.

Epigentics may have important implications for the treatment of cancer. The cell-based functional profiling platform has the capacity to measure genetic and epigenetic events as a functional, real-time adjunct to static genomic and proteomic platforms.

By examining small clusters of cancer cells (microspheroids or microclusters) in their native state, it can provide a snapshot of the response of tumor cells to drugs, combinations and targeted therapies.

The proteomic platform does not clarify how the response to targeted drugs compares with that to chemotherapy, combinations, or other targeted therapies. There is a challenge to identify which patients the targeted treatment will be effective.

The analysis is unique in that each microspheroid examined contains all the complex elements of tumor biosystems found in the human body and have a major impact on clinical response. Cell function analysis is a conduit that connects novel drugs to clinicians and patients in need.

Sources:

Nagourney RA, Kollin CA, Sommers B, Su Y-Z, Evans SS. Functional profiling of human tumors in primary culture: a platform for drug discovery and therapy selection, AACR abstract #1546, 2008

Weisenthal Cancer Group, Huntington Beach, CA and Departments of Clinical Pharmacology and Oncology, Uppsala University, Uppsala, Sweden. Current Status of Cell Culture Assay Testing May, 2002.

Functional profiling with cell culture-based assays for kinase and anti-angiogenic agents Eur J Clin Invest 37 (suppl. 1):60, 2007

Functional Profiling of Human Tumors in Primary Culture: A Platform for Drug Discovery and Therapy Selection (AACR: Apr 2008-AB-1546)

kayandok
Posts: 1223
Joined: Jun 2008

thank you sharing this infomation. I'm sure it is all the chemo I had yesterday, but are their methods of testing are not necessarily helpful for patients with mets?
kathleen

gdpawel's picture
gdpawel
Posts: 545
Joined: May 2001

Kathleen

As I mentioned above, regular biopsies are needed in recurrent ovarian cancer patients (that's true with any type of cancer). Going after a surgical/biopsy specimen has a role in eliminating ineffective agents and avoid unnecessary toxicity and in directing "correct" therapy.

The time and energy required to conduct an excisional biopsy pales in comparison to the time, energy and lost opportunities associated with months of ineffective, toxic therapy.

Patients would certainly have a better chance of success had their cancer cells 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 (targeted or conventional) would be more likely to improve survival.

It would seem more prudent to invest the time in using diagnostic technologies for detecting cancer growths, as well as the properties of cells that are destined to metastasize, and match the most "effective" therapeutics to your "indivdual" cancer cells (not from some average population study).

Greg

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