drugs already approved indirectly attack breast cancer stem cells (responsible for bc

Lani · 01-18-2011, 09:29 AM

growth and spread).
I heard much about this at last year's AACR annual conference in Washington, DC in APril

Now it has been published(and via open access):

U-M researchers find indirect path to attack breast cancer stem cells
[University of Michigan Health System]
ANN ARBOR, Mich. — Scientists at the University of Michigan Comprehensive Cancer Center have identified a potential new way of attacking breast cancer stem cells, the small number of cells in a tumor that fuel its growth and spread. Researchers found that breast cancer stem cells are regulated by a type of cell derived from bone marrow, called mesenchymal stem cells. These cells are drawn from the bone marrow to the cancer and create a "niche" for the cancer stem cells, allowing them to replicate.

"The importance of this is that we may be able to attack breast cancer stem cells indirectly by blocking these signals from the niche," says study author Max S. Wicha, M.D., Distinguished Professor of Oncology and director of the University of Michigan Comprehensive Cancer Center.

Breast cancer stem cells were first identified by Wicha and colleagues at the University of Michigan in 2003. Cancer stem cells are believed to be resistant to current chemotherapies and radiation treatment, which researchers say may be the reason cancer so often returns after treatment.

Little is known about the cancer stem cell niche - a type of microenvironment that is highly associated with tumor growth and metastasis. The researchers looked at mesenchymal stem cells, which arise in bone marrow. They found that breast cancers in mice sent out signals which attracted mesenchymal stem cells from the bone marrow into the tumor where these cells interacted and stimulated the growth of breast cancer stem cells.

Researchers then identified two signals from a cytokine network - a type of protein that affects how cells communicate - that were responsible for stem cell regulation. These same cytokines play a role in inflammation and drugs that block them have already been approved for the treatment of inflammatory diseases such as rheumatoid arthritis. By blocking these cytokine signals, researchers hope that they can successfully target the cancer stem cell population providing a more effective treatment for breast cancer.

Results: of the study appear in the Jan. 15 issue of Cancer Research.

Additional authors: From U-M: Suling Liu, Sing J. Ou, Shawn Clouthier, Shivani H. Patel, Hasan Korkaya, Amber Heath, Julie Dutcher, Celina G. Kleer, Younghun Jung, Gabriela Dontu, Russell Taichman; from Centre de Recherche en Cancerologie de Marseille: Christophe Ginestier

Funding: National Institutes of Health, Taubman Research Institute

Disclosure: Wicha has financial holdings in OncoMed Pharmaceuticals, which has applied for a patent on cancer stem cell technologies.

OPEN ACCESS: Breast Cancer Stem Cells Are Regulated by Mesenchymal Stem Cells through Cytokine Networks
[Cancer Research]
We have used in vitro and mouse xenograft models to examine the interaction between breast cancer stem cells (CSC) and bone marrow-derived mesenchymal stem cells (MSC). We show that both of these cell populations are organized in a cellular hierarchy in which primitive aldehyde dehydrogenase expressing mesenchymal cells regulate breast CSCs through cytokine loops involving IL6 and CXCL7. In NOD/SCID mice, labeled MSCs introduced into the tibia traffic to sites of growing breast tumor xenografts where they accelerated tumor growth by increasing the breast CSC population. With immunochemistry, we identified MSC-CSC niches in these tumor xenografts as well as in frozen sections from primary human breast cancers. Bone marrow-derived MSCs may accelerate human breast tumor growth by generating cytokine networks that regulate the CSC population.

Rich66 · 01-20-2011, 07:08 AM

Quote:

Researchers then identified two signals from a cytokine network - a type of protein that affects how cells communicate - that were responsible for stem cell regulation. These same cytokines play a role in inflammation and drugs that block them have already been approved for the treatment of inflammatory diseases such as rheumatoid arthritis.

Ok...which drugs?

Ellie F · 01-20-2011, 08:43 AM

I was wondering to!
Any idea Lani?

Thanks
Ellie

Trish · 01-20-2011, 03:44 PM

I'd love to know too. I think I could develop rheumatoid arthritis.... Thanks Trish

Chelee · 01-20-2011, 04:39 PM

I would love to know which drugs also?

Chelee

Rich66 · 01-24-2011, 12:18 AM

And so...

Jackie07 · 01-24-2011, 04:57 AM

http://arthritis.about.com/od/inflam.../cytokines.htm

Ellie F · 01-24-2011, 05:04 AM

Thanks Jackie.
Makes you wonder,I have known a great many ppl on these types of drugs who never seem to develop cancer.

Ellie

Joan M · 01-24-2011, 07:54 AM

Perhaps Rituxan (rituximab) is one such drug. This drug is used for certain types of non-Hodgkin's lymphoma, but also I believe for rheumatoid arthritis and is also an anti-inflammatory. I understand that cancer involves inflammation of a sort.

And Rich, you're right. Shoddy reporting.

Joan

02-04-2011, 08:54 PM

http://www.cancer.med.umich.edu/news...atment10.shtml

Repertaxin blocks interleukin 8 and interrupts a critical signal that allows breast cancers cells to grow. This may not be one of the drugs mentioned in the article you folks are discussing. But perhaps still useful information, so I wanted to make it available to you.

I'm not a cancer patient or a cancer survivor. I do in depth research related to investing in biotech and have a science background. I just happened onto your website while investigating the relationship between cancer stem cells and pro-inflammatory cell signalling.

Another already approved drug worth looking at is itraconazole. It's an anti-fungal that has been found to block the SHH pathway, which appears to play a role in cancer stem cell growth.

http://www.reyalab.org/manage/user_f...1274278169.pdf

Best to all.

Trish · 02-05-2011, 03:19 AM

Thanks everyone.
Trish

Ellie F · 02-05-2011, 04:44 AM

Thanks to all and to unregistered for your interest. It's often good to have different perspectives.

Ellie

das · 02-05-2011, 07:26 AM

Do you think this is related to the reported decreased risk of recurrence associated with NSAIDs use?
http://www.ncbi.nlm.nih.gov/pubmed/17404892

kiwigirl · 02-06-2011, 06:16 AM

What about dexamethasone (Decadron) as this used for rheumatoid arthritis and reduces inflammation.

Rich66 · 02-06-2011, 10:36 AM

Ah..I remember the Repertaxin/Il-8 article by Wicha. Searching on it today, now called Reparaxin, but still investigational:
http://www.biocentury.com/products/reparixin

Hadn't heard of the Itraconazol. But yes..it's available!
Joan, did you have some for the fungal ball? Seems like one might be able to justify some based on relatively common nail fungi:
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000916

Not sure which form (pill, solution) would be best for off label cancer use.

AlaskaAngel · 02-06-2011, 11:29 AM

As long as we are speculating... (DebbieL, where are you?)

I have long wondered whether the supposedly beneficial effects of chemotherapy had more to do with the support drugs given during chemotherapy than they did with the chemotherapy, since trials do not separate those effects out. Is the torture of chemotherapy getting the "credit" for beneficial effects that are in reality provided by other drugs? Is the chemo essential, or not?

Is it the anti-inflammatory effects of steroids (that are given in order for the body to better tolerate such toxic therapy) the real workhorses that provide the initial magic of nonrecurrence, for example? And at the same time, do they start a chain of events that encourage recurrence farther down the road, such as from slower metabolism and greater weight gain? And how dependent are they on one's stage of development for their results -- favorable or unfavorable?

Maybe if endocrinologists were more involved in the understanding and application of our treatment we would have a more disciplined scientific approach to it.

AlaskaAngel

Joan M · 02-06-2011, 05:39 PM

Rich,

Yes, I did. When I had the fungal ball, or mycetoma, in my lung, I took voriconazole, which is an advanced form of itraconazozle. I then came across an article last spring about itraconazole's potential use in blocking the Hedgehog pathway in cancer. I sent an e-mail to the scientist doing the research, asking whether voriconazole would have the same effect. Here's his answer (which I really appreciated, as he took the time to explain it):

Please be aware that I am not clinically trained and cannot advise you on your medical condition.

In response to your question, our article described an effect of itraconazole on the Hedgehog signaling pathway, which plays an important role in organizing the normal pattern of embryonic growth and development, and also can play a role in the abnormal growth of certain tumors.

The effect of itraconazole on Hedgehog signaling is by a mechanism distinct from its effect on fungal growth. Other antifungal drugs, including voraconazole (Vfend) act on fungal growth by a mechanism similar to that of itraconazole but, unlike itraconazole, do not efficiently inhibit the Hh pathway. We specifically tested several other azole antifungals (the class of drug that includes itraconazole and voraconazole) and saw little effect if any on Hedgehog signaling (voraconazole was completely inactive in affecting the Hedgehog pathway).

To help you think about this, imagine two keys that have similar shafts and can both open the same lock, but have very different bows (the part you hold when you are turning the key). In this analogy, the effect of itraconazole on the Hh pathway is due to the structure of the bow. Voraconazole is also able to inhibit fungal growth because it has a similar shaft, but not the Hedgehog pathway because the bow is very different.

I would therefore not expect your treatment with Vfend to have had much or any effect on the Hedgehog pathway. A separate question is what role the Hedgehog signaling pathway may have in breast cancer. I cannot answer that question, although we are interested and have attempted to obtain funding to study it (with no success thus far).

I hope this helps. I wish you all the best.

*****
I was hoping to get a lucky break since I took Vfend for four months. Genetech is also studying the Hedgehog pathway in breast cancer.

Joan