cancer stem cells: anyone talking about it?

[Rich66]

Is anyone here talking to their oncs about CSCs and how it might direct their treatment?

I sent an e-mail to a researcher and thought I would share an excerpt with you folks.


I have collected a number of articles and abstracts that inform my thoughts/questions and have posted a number of them here:
http://her2support.org/vbulletin/showthread.php?t=38953
and
http://her2support.org/vbulletin/showthread.php?t=39323

I am definitely interested in the recent Perifosine results and wonder if it is being used off-label for breast cancer.

Tranilast, available in Japan as seemingly safe anti-allergic, seems like it might have effects on CSCs. I see Nuon Inc has some trials for arthritis but nothing for cancers. Thoughts?

Is there any kind of list regarding currently available therapies that inhibit CSCs as opposed to aggravating them. One of my strongest concerns is how to proceed with currently available therapies without promoting CSC responses. Outside of trials, I am only aware of MAB agents with (presumed*) limited application such as Herceptin or Lapatinib that work this way.
Are there available agents that are thought to address the non-CSC population without aggravating CSCs?
I have read that CSCs are thought to be ER- and HER2 +. *Is there gathering momentum to the idea of treating most BC as such or at least to include components that address this baseline/underlying subset?

I have come across suggestion that Tamoxifen has an effect on ER- cells. Perhaps this could be useful in addressing CSCs as well as the tumor bulk in broadly ER+ tumors?

With the notion of the influence of mesenchymal stem cells being a part of the CSC equation, does that help explain the benefit of bisphosphonates such as Zoledronic acid alone or shortly after chemo?

Some have suggested external beam radiation post surgery has inherent limits in dosage which may prevent killing of CSCs. Is there any thought as to whether focused treatments like cyberknife deliver an adequate dose to CSCs? Similarly, has there been any investigation into Yttrium 90 (SIR spheres) or other brachytherapy approaches as to whether they deliver enough radiation to kill CSCs?

Finally, Is there an available serum test to monitor CSCs in patients?

[StephN]

Hi Rich -
You must have read my mind. I was looking at some of this same research while deciding whether to discontinue my Herceptin last Dec. I had planned to bring it up again with my med onc when I see her tomorrow.
There are so many new pieces to the puzzle of this disease, that I am not really sure that I should remain off the drug.
I do feel better and have more energy, so would like to believe that having had SO MUCH Herceptin has killed off the stem cells. However it is early days in this research and my odds may not be as good as I was hoping.

[bejuce]

Hi Rich,

I've been diligently following your stem cell thread with much hope for newer targeted therapies. I've asked my oncologist about them but her opinion is that it's still early on to have much of an effect on patients like me undergoing active therapy. I'm still undergoing neoadjuvant chemo and had my 3rd Taxotere dose today (one more to go!). I'll stop the Tykeb in July and start Herceptin the day after before having my surgery sometime in August. I hope that when I'm done with Herceptin next year I'll be able to take another drug (a pill?) that will specifically target the stem cells. The research makes sense to me and I believe there should be more besides Herceptin and Tykerb coming our way.

Thanks for your continued postings on this - I've learned much fom them.

[Rich66]

Bjuce: Good luck with the neo-adjuvant. Looks like you are swinging hard from the beginning.

Steph: Your situation is actually one that makes me wonder if teh CSC paradigm is missing a few pieces. or thta they should identify combinations of existing "old school" therapies that get at the CSCs. Harder to get funding for retrospective research I bet. I'd be curious about test to check your CSCs

[StephN]

Hi Rich -
All my bloodwork and scans looked so good at today's meeting with onc that we did not feel a need for CTC test. The HER2 serum was not yet back, but we do not feel that is the most important indication of active cancer in my case.

Her comment on the stem cell death issue was that there is no proof that I may not still have some of those little devils lurking in my body. But the amount of Herceptin I had makes it likely that there is no threat now.

She did not feel that going over to Tykerb as a prophylactic measure just now would be of proven benefit.

So I sit tight and coast for another 3 months.

[Rich66]

although it seems to be of help, I don't know if CTC is the same as a "CSC test". I think there are markers such as CD44 and aldehyde dehydrogenase 1 (ALDH1) that can be tested for.
http://jco.ascopubs.org/cgi/content/full/26/17/2795
http://breast-cancer-research.com/content/8/4/R41

But I was thinking it would be interesting to see if they couldn't find any CSCs in you. Because...the thought seems to be that current conventional therapies don't kill CSCs. But based on cases like yours, I wonder if certain combinations do. Or maybe there is something unique to your biology that made conventional therapies work better.

[StephN]

I see what you mean - I did not ask about any kind of blood test for Circulating stem cells. There may be such a thing used in esoteric research, but not in general patient use.

I can ask my med onc and see how she thinks such tests could differ in what they read.

There is always the question of the actual MUTATION being gone as well, or my immune system learned to recognize it. This is something that I came across at the AACR meeting.

[Rich66]

There is a chart/list of CSC markers in Table 2 of :
http://jco.ascopubs.org/cgi/content/full/26/17/2795

Anyone else bringing this up to their Oncs?

[Rich66]

It's clear we need a treatment paradigm shift. Anyone bringing this up to their oncs.?

[StephN]

Hello Rich -
Finally got a moment where I could concentrate on the article in the link above.
VERY INTERESTING! Goes much deeper into the science of what we have been dancing around in this thread.

The article is pointing out the need to develop therapies to target the STEM CELLS, which have different properties than the active cancer cells conventional agents are going after.

Those properties being 'quiescenc," or the ability to lay low for a long period of time, and resistence.

Being so strongly HER2 positive has worked in my favor, I believe. Also, not having the added complication of being hormone positive. The Herceptin could hopefully attach to the stem cells and sit there shutting down their receptors until the cells finally died their natural death, however long that might take.

I will ask my med onc about those breast cancer stem cells markers mentioned in that article.

[StephN]

Answer on breast cancer stem cells serum test:

"There aren't currently any commercially available tests for cancer stem cells, it's all still research."

This was my impression from talking to a few people at the American Association of Cancer Researchers meeting last April in Denver. These marker tests take YEARS, even DECADES to gain acceptance and approval. Just because they are mentioned in a study des not mean my oncologist has access to it, as much as I would like it. If the results are not accurate or reliable then such a test would just confuse my decisions.

[Rich66]

Interesting interview with CSC guru that discusses assays:
http://www.nature.com/stemcells/2009...s.2009.47.html

Here's a link to a test:
http://www.stemcell.com/technical/aldh.aspx

The ALDEFLUOR® and ALDECOUNT® reagent systems offer a novel approach to the identification, enumeration and isolation of stem cells and progenitor cells based on aldehyde dehydrogenase (ALDH) enzyme activity. ALDH is highly expressed by stem and progenitor cells of various lineages, including hematopoietic, endothelial, mesenchymal, neural and mammary.1-