Ovarian cancer not just one disease, study finds

Ovarian cancer not just one disease, study finds

Treatment for often-fatal illness may change as a result

The Vancouver Sun
Tue 02 Dec 2008
Page: A5
Section: Westcoast News
By: Pamela Fayerman

Ovarian cancer is actually different diseases with five distinct subtypes, an international team led by Vancouver scientists has shown. The team drew its conclusion after molecular analysis of centrally banked tumour tissue samples from 500 B.C. women who got ovarian cancer over 25 years, many of whom died. Their findings help explain why the majority of women diagnosed with such cancer die -- not only is the disease being diagnosed too late, but the stock approach to treatment has been ineffective since ovarian cancer is not a "monolithic entity."

"We've had one recipe, which is usually surgery followed by the same chemotherapy, irrespective of the tumour type, because we didn't know any better," said study co-author Dr. Dianne Miller of Vancouver General Hospital and the B.C. Cancer Agency. "So to me, as an oncologist working in ovarian cancer for the past 18 years, the impact of this study means everything," she said. "In the past, we've bundled everything together and haven't exploited the differences in tumour types but as a result of this research, we can treat patients differently because subtypes have unique [molecular characteristics]," Miller added.

In the three-year study, published today in PLoS (Public Library of Science) Medicine, the researchers identified 21 biomarkers -- molecular characteristics exhibited by tumours in each subtype. Subtypes respond differently to chemotherapy and treatment regimens are already starting to change because the researchers have been sharing their discoveries at meetings around the world. "All too often, ovarian cancer is lethal, but what we've shown in this research is that if you are going to fight the battle, you must fight it one subtype at a time," said lead author Dr. David Huntsman, a pathologist at the cancer agency and VGH. "And this paper sets a new course because you can't change treatment until you change research."

Since some subtypes are rare, Huntsman said he hopes scientists globally collaborate and share resources. The biomarkers are not "100-per-cent ready for prime time" to be used as routine diagnostic markers, he said. Huntsman said the work moves ovarian cancer research to a place where other cancer researchers were a few decades ago when they realized that leukemias and lymphomas had many subtypes. That paved the way to tailored diagnostic tests and treatments, which have been a boon to improving survival odds. University of B.C. medical school dean Gavin Stuart, an ovarian cancer expert who was not involved in the study, said subtyping is akin to an "analysis of handwriting in identifying individual persons. "This allows us to better understand the optimal approach to therapy in women affected by this disease."

About 200,000 women around the world (2,400 in Canada) get ovarian cancer every year and more than half die from the disease. If the cancers are detected in the earliest stages, about three-quarters of the women may survive to five years, but the vast majority are diagnosed when the cancers have spread into the pelvis, stomach and liver or to distant areas like the brain. In such cases, the death rate is 85 per cent at five years. The research was funded by the Canary Foundation, BCCA, VGH and UBC Hospital Foundation, Vancouver Coastal Health Research Institute and by unrestricted grants from Eli Lilly and sanofi aventis pharmaceutical companies.

By NotDyingToday
Posted December 3, 2008 at 10:35 am
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This is why we might all want to start taking a closer look at the customized treatments being developed now--some of which are in clinical trials. I'm enrolled in one at the University of Pennsylvania . This trial involves the development of a PERSONALIZED VACCINE USING A WOMAN'S OWN TISSUE. This trial is for women with recurrence. Tumor tissue is collected during a debulking and then used to make the vaccine. To learn more go to http://www.ocvi.org/
and
http://www.oncolink.org/resources/article.cfm?c=3&s=39&ss=229&id=960

By JanP
Posted December 3, 2008 at 5:50 pm
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This is very interesting but I suppose too late for those of us who already have ovca. I mean how can they find out what specific sort of cancer we have?
Perhaps a biopsy of new tumours? My new ones are not operable as too near main blood vessels, but I'll certainly remember this new reseach if I get more tumours which can be biopsied!
Can anyone explain why someone would ask to be
"my Friend" and how to do it?
JanP

By Sharlene
Posted December 3, 2008 at 6:01 pm
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I think JanP it is to let anyone know that they are important to all of us .Possibly you have a concern you may not want to share with everyone but just a friend.You also have the right to delete such friend for whatever reason as this is your site and your life.
You do it by following the steps "to meet a friend".
Angel Hugs,
Sharlene

By Hil323
Posted December 4, 2008 at 1:46 pm
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I'm interested in the fact that it's just British Columbian Women. Genetically, it would make sense that they were similar, for the most part. There really needs to be a bigger study done before everyone jumps on the band wagon. But thank GOODNESS someone is doing research!

By Jennali
Posted December 5, 2008 at 8:34 pm
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When I complained to my gyn/onc the other day that treatment seemed such a crap shoot, he said that the kind of individualized drug cocktails we need to be using are probably 20 years away.

Maybe if more research like you posted gets done, that 20 years will shrink.

By gpawelski
Posted December 6, 2008 at 10:22 am
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To beat down cancer mortality, oncologists need to target all the many cancers that make up a cancer - the dozens of different pathways that cells use to proliferate and spread. That is the leading edge of research today, determining how this patient’s tumor cells work and hitting those pathways with multiple drugs, simultaneously or sequentially, each chosen because it targets one of those growth, replication and angiogenesis pathways. The hope is to match tumor type to drug. We need to make the next leap, getting the right drug to the right patient.

Cancer cells often have many mutations in many different pathways, so even if one route is shut down by a targeted treatment, the cancer cell may be able to use other routes. In other words, cancer cells have “backup systems” that allow them to survive. The result is that the drug does not shrink the tumor as expected. One approach to this problem is to target multiple pathways in a cancer cell.

The key to understanding the genome is understanding how cells work. The “cell” is a system, an integrated, interacting network of genes, proteins and other cellular constituents that produce functions. You need to analyze the systems’ response to drug treatments, not just one target or pathway. Another challenge is to identify for which patients the targeted treatment will be effective. Screening compounds for efficacy and biosafety.

Tumors can become resistant to a targeted treatment, or the drug no longer works, even if it has previously been effective in shrinking a tumor. Drugs are combined with existing ones to target the tumor more effectively. Most cancers cannot be effectively treated with targeted drugs alone. You need to measure the net effect of all processes within the cancer, acting with and against each other in real time, and test living cells actually exposed to drugs and drug combinations of interest.

Multi-targeted drugs can be well-predicted by measuring the effect of the drugs on the function (is the cell being killed regardless of the mechansim) of live cells, as opposed to a target (does the cell express a particular target the the drug is supposed to be attacking). While targeted screening tells you whether or not to give one drug, functional screening can find other compounds and combinations and can recommend them from the one analysis.

By patsybee
Posted December 6, 2008 at 11:13 am
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My doctor yesterday told me that they keep tissue samples in parafin, but can those be used for research?

I am currently on Avastin and Cytoxan and my tumors are shrinking, but the doctor told me yesterday that I really can't expect a remission from that because only 20% have that result. I need to get into remission in order to qualify for a clinical trial at Stanford for a vaccine. He said he could put me on another drug that would be more likely to give me a remission and that the Avastin was to give me a rest from the chemo, mostly. I don't know what to do.

Patsybee

By gpawelski
Posted December 6, 2008 at 6:31 pm
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Patsybee. Some scientists suggest research be performed on the paraffin-embedded tissue specimens which - commonly are used in pathology labs instead of fresh frozen specimens that need special equipment - would enable the technology to be used at the community-hospital level, instead of being confined to comprehensive cancer centers and teaching hospitals.

However, gene expression in paraffin embedded tissue can change over time. Also, although validation studies were designed prospectively, sampling biases may exist when using old stored tissue. So, tissue that is exposed to paraffin embedded, fixed, minced, or frozen, is no longer is useful.

One gets more accurate information when using intact RNA isolated from fresh tissue than from using degraded RNA, which is present in paraffin-fixed tissues (preserved in paraffin wax). Established cell lines have been conclusively proven to have no predictive value at all with respect to clinical activity. In the laboratory, these cells are highly resistant to anti-cancer drugs. An established cell line is not reflective of the behavior of fresh tumor cells in primary culture in the lab, much less in the patient.

By Brandi
Posted December 12, 2008 at 1:42 am
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Thank you all so much for sharing this information that you have learned. I just finished treatment for OvCA IIIC in May and so far am cancer free but dread the day that it reappears. I wish all of you the very best in dealing with this disease. Hopefully we can all benefit from the advances that the researchers are making. Hang on and be strong!

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