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Old 08-18-2011, 08:55 PM   #1
Rich66
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The future of cancer lies behind us

http://www.youtube.com/watch?v=mAGhNhrHMJs

Robert A. Nagourney, MD, is Medical and Laboratory Director at Rational Therapeutics, Inc., in Long Beach, California, and teaches Pharmacology at the University of California, Irvine School of…
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Old 08-20-2011, 11:18 AM   #2
gdpawel
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Re: The future of cancer lies behind us

When I heard Dr. Nagourney talk about "venture capitalists," I truely knew what he was talking about. I don't know if anybody knows or remembers, Drs. Nagourney and Larry Weisenthal had started Oncotech in 1985. They each left Oncotech in 1991, free of the constraints of the venture capitalists who ended up in control of Oncotech. They each left over disagreements with the controlling investors (4 venture capital companies) over management and directions of the company (mainly staying with the cell-growth assay). Oncotech closed last year after being taken over by Exiqon, a multi-national company, stolen of the vast collection of slides, and spit out. Certainly glad they got out when the getting out was available.
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Old 08-20-2011, 11:47 AM   #3
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Re: The future of cancer lies behind us

No disrespect intended, but I wonder if more could be accomplished if the two had explicitly joined forces post Oncotech.
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Old 08-20-2011, 02:31 PM   #4
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Re: The future of cancer lies behind us

I often thought about that Rich. The one is the ying to the others yang. I imagine the taste of venture capitalists probably soured the thought of it.
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Old 08-20-2011, 02:47 PM   #5
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Re: The future of cancer lies behind us

Sounds like they might attract a lot of Chinese investment
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Old 08-20-2011, 02:59 PM   #6
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Re: The future of cancer lies behind us

LOL!

With the most recent study published in the Journal of Translational Medicine, "Peritoneal carcinomatosis from ovarian cancer: chemosensitivity test and tissue markers as predictors of response to chemotherapy," which was a clinical trial finding personalized cancer cytometrics more accurate then molecular gene testing, someone had asked me, "what labs are doing Personalized CCT's?"

Cell culture assay testing is done universally around the globe. It is not just some U.S. thing. These clinicians get together on their own little forum and discuss the in's and out's of their technology. Unfortunately, they have come together and decided on a new name for "chemosensitivity testing." They decided to call it "personalized cancer cytometrics." It wasn't unanimous, but none-the-less, the majority ruled, so Personalized Cancer Cytometrics it is.

Cytometrics literally means measuring cells. Accurate. The problem was that there were so many terms being used that one couldn't search the literature using a single keyword phrase. So they've been trying to agree on something universally acceptable for several years, and this is where they are. It's at least as accessible to lay people as "positron emission tomography" (PET).

Now, as to what labs do Personalized CCT's? This particular study was done in Italy. These tests are done throughout Europe, China, Japan, Thailand, etc., as well as here in the U.S. What I do know is this particular study was done with the "gold standard" of chemosensitivity testing: "cell-death" assay.

I'm sure Chinese venture capitalist have already invested in their own assay labs.
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Old 08-20-2011, 03:22 PM   #7
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Re: The future of cancer lies behind us

Good talk, and he might be right. I don't know enough to say. However, Herceptin was developed by studying cancer genes.
__________________
Amy
_____________________________
4/19/11 Diagnosed invasive ductal carcinoma in left breast; 2.3 cm tumor, 1 axillary lymph node, weakly ER+, HER2+++
4/29/11 CT scan shows suspicious lesions on liver and lungs
5/17/11 liver biopsy
5/24/11 liver met confirmed--Stage IV at diagnosis
5/27/11 Begin weekly Taxol & Herceptin for 3 months (standard of care at the time of my DX)
7/18/11 Switch to weekly Abraxane & Herceptin due to Taxol allergy
8/29/11 CT scan shows no new lesions & old lesions shrinking
9/27/11 Finish Abraxane. Start Herceptin every 3 weeks. Begin taking Arimidex
10/17/11--Brain MRI--No Brain mets
12/5/11 PET scan--Almost NED
5/15/12 PET scan shows progression-breast/chest/spine (one vertebra)
5/22/12 Stop taking Arimidex; stay on Herceptin
6/11/12 Started Tykerb and Herceptin on clinical trial (w/no chemo)
9/24/12 CT scan--No new mets. Everything stable.
3/11/13 CT Scan--two small new possible mets and odd looking area in left lung getting larger.
4/2/13--Biopsy of suspicious area in lower left lung. Mets to lung confirmed.
4/30/13 Begin Kadcyla/TDM-1
8/16/13 PET scan "mixed," with some areas of increased uptake, but also some definite improvement, so I'll stay on TDM-1/Kadcyla.
11/11/13 Finally get hormone receptor results from lung biopsy of 4/2/13. My cancer is no longer ER positive.
11/13/13 PET scan mixed results again. We're calling it "stable." Problems breathing on exertion.
2/18/14 PET scan shows a new lesion and newly active lymph node in chest, other progression. Bye bye TDM-1.
2/28/14 Begin Herceptin/Perjeta every 3 weeks.
6/8/14 PET "mixed," with no new lesions, and everything but lower lungs improving. My breathing is better.
8/18/14 PET "mixed" again. Upper lungs & one spine met stable, lower lungs less FDG avid, original tumor more avid, one lymph node in mediastinum more avid.
9/1/14 Begin taking Xeloda one week on, one week off. Will also stay on Herceptin and Perjeta every three weeks.
12/11/14 PET Scan--no new lesions, and everything looks better than it did.
3/20/15 PET Scan--no new lesions, but lower lung lesions larger and a bit more avid.
4/13/15 Increasing Xeloda dose to 10 days on, one week off.
7/1/15 Scan "mixed" again, but suggests continuing progression. Stop Xeloda. Substitute Abraxane every 3 weeks starting 7/13.
10/28/15 PET scan shows dramatic improvement everywhere. All lesions except lower lungs have resolved; lower lungs noticeably improved.
12/18/15 Last Abraxane. Continue on Herceptin and Perjeta alone beginning 1/8/16.
1/27/16 PET scan shows cancer is stable.
5/11/16 PET scan shows uptake in some areas that were resolved on the last two scans.
6/3/16 Begin Kadcyla and Tykerb combination
6/5 - 6/23 Horrible diarrhea from K&T together. Got pneumonia.
7/15/16 Begin Kadcyla only every 3 weeks.
9/6/16 Begin radiation therapy on right lung lesion that caused the pneumonia.
10/3/16 Last of 12 radiation treatments to right lung.
11/4/16 Huffing and puffing, low O2, high heart rate, on tiniest bit of exertion. Diagnosed as radiation pneumonitis. Treated with Prednisone.
11/11/16 PET scan shows significant improvement to radiated part of right lung BUT a bunch of new lung lesions, and the bone met is getting worse.
11/22/16 Begin Eribulin and Herceptin. H every 3 weeks. E two weeks on, one week off.
3/6/17 Scan shows progression in lungs. Bone met a little better.
3/23/17 Lung biopsy. Tumor sampled is ER-, PR+ (5%), HER2+++. Getting Herceptin and Perjeta as a maintenance treatment.
5/31/17 Port placement
6/1/17 Start Navelbine & Tykerb
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Old 08-20-2011, 03:36 PM   #8
Rich66
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Re: The future of cancer lies behind us

They should outsource to the US since our Dr. Ying and Dr. Yang have a head start. They might somehow have some latent Mandarin vocabulary.
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Old 08-20-2011, 06:22 PM   #9
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Re: The future of cancer lies behind us

Amy

Targeted drugs are specifically designed to block one or more critical pathways involved in cancer-cell growth and metastases. The development of these therapies stems from advances in molecular biology that have permitted the identification of qualitative and quantitative differences in gene expression between cancer cells and normal cells.

However, there are lots of things which determine if drugs work, beyond the existence of a given "target." Does the drug even get into the cancer cell? Does it get pumped out of the cell? Does the cell have ways of escaping drug effects? Can cells repair damage caused by the drug? Do combinations of drugs work in ways which can't be predicted on the basis of static gene expression patterns?

Tumor biology is a lot more complex than we'd like it to be. Cancer is more complex than its gene signature. Many common forms of cancer present as a host of mutated cells, each with a host of mutations. And they're genetically unstable, constantly changing. That's why so many cancers relapse after initially successful treatment. You kill off the tumor cells that can be killed off, but that may just give the ones that are left a free reign.

The idea of searching for clinical responders by testing for a single gene mutation seems nice, but as we've seen with Herceptin, you may have to test for dozens of protein expressions that may be involved in determining sensitivity/resistance to a given drug. Because if you miss just one, that might be the one which continues cancer growth.

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.

Greg
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Old 12-14-2011, 06:09 PM   #10
gdpawel
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Symposium on Circulating Tumor Cells and Chemosensitivity Testing

Rich

Symposium on Circulating Tumor Cells and Chemosensitivity Testing
Santa Monica, December 7–9, 2011

Robert Nagourney, MD, founder of Rational Therapeutics, Inc., Long Beach, CA, was a featured speaker at The Symposium on Circulating Tumor Cells and Chemosensitivity Testing, December 7 – 9, at Loews Beach Hotel, Santa Monica, CA.

The academic conference was sponsored by the Angeles Clinic Foundation, as a result of a generous gift from the Farrah Fawcett Foundation. Fawcett died in 2009 at St. John’s Health Center after a lengthy battle against cancer, but was a believer in what is being called Personalized Cancer Cytometrics -- a decision by investigators in the field, who decided that they should actually come up with a name which everyone will agree to use.

This was the first symposium of it's kind to be offered in the world and the development of this type of technology was the hope and dream of Farah Fawcett whose foundation has supported the development of this symposium. Ms. Fawcett had chemotherapy through the John Wayne Cancer Institute of which The Angeles Clinic is affiliated.

The invitation only symposium brought together the world’s prominent researchers in this area in order to raise awareness and explore current methods of cancer treatment including assays. Although the symposium was a very closed affair, a formal "White Paper" is being produced and a there may be a formal peer-reviewed publication coming out of it.

Dr. Nagourney, a board certified oncologist and hematologist and noted expert on chemosensitivity testing for more than 20 years, will highlight the lack of progress made in this arena due in part to the politics and economics of cancer treatment. “Physicians tend to follow standardized guidelines or ‘off the shelf treatments’ that provide the same traditional chemotherapy agent to every cancer patient. The treatments work adequately well, the schedules are established, the toxicities are well known, and no one is cured.”

Dr. Nagourney, who recently addressed the situation at a TEDx symposium, sees an overwhelming need to spread the message this conference addressed – using cell-death cell culture assays, which provide a functional profile of how the cancer will respond to treatment.

Dr. Nagourney says, “Combining diagnostic skill with scientific insight, the physician becomes the captain of the ship.” He adds that assay-directed approaches can provide objective data that is then used to guide treatment selections. “Predicated upon an understanding of the patient’s tumor biology, cancer therapy becomes an intellectual exercise that draws upon literature and a knowledge of pharmacology and physiology,” he says.

HealthNewsDigest.com

As there had been a death in my family, my ability to attend the entire conference was limited and I could only particpate the afternoon session. The symposium included several areas of investigation, including circulating tumor cell analysis, molecular profiling and functional analytic platforms. I had the opportunity to sit in on several presentations including one by Dr. Weisenthal, who gave an overview of his seminal contributions to the field followed by his discussion of his work on VEGF inhibition and the crosstalk between other classes of tyrosine kinase inhibitors and endothelial (vascular) cell viability. Dr. Presant gave a presenation on their work with the MiCK assay, with a focus upon leukemia studies and their developing work on solid tumors. My impression is that we made a fundamental transition. In the past I was repeatedly confronted by oncologists who said: ”We could not do this.” Today the question appears to be more: “How best can we do this?" In that regard there has been progress. - Robert Nagourney
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