Scientific American Article By The World Expert On Breast Cancer Stem Cells

[Lani]

He is the one who asked that the her2group advocate for change to the medical privacy laws as they apply to cancer research. An easier way to accomplish the same thing would be for all the participants on this site to give permission to utilize a tiny portion of their surgical specimens for his research and wave their rights to privacy--wouldn't you want to know what genes and proteins and receptors are on YOUR individual tumors? Perhaps Cynthia can comment on the legality of all this, but the Wall St Journal article on the woman with the lung disease I posted within the last couple of weeks indicated she got others with her disease to donate material for the researchers to work on. Only very tiny amounts are necessary for microarray work, so there would be lots left over if better techniques become available to study your tumor later...

THIS article is written for the general public. The part about inflammatory signals causing the migration and division of stem cells(eg, after surgery) is especially well-described and thought-provoking. I await their theories on how radiation therapy alters the picture.

This article is REALLY WORTH THE EFFORT TO READ...and THINK about its consequences. Among the big questions in my mind are:

is her2 on the stem cells?
are ER and/or PR on the stem cells?

Here is the link(?):
http://www.scientificamerican.com/ar...0A83414B7F0000

[chrisy]

Thought provoking article, Lani
another question which comes to mind, is there an identifiable factor present in the cancer stem cell which could be targeted much as Herceptin targets Her2, disabling the stem cell without damaging normal stem cells? I thought I read that one such factor had been identified.
Thanks for the post.

[Lani]

to look for those properties/receptors/unique properties on CANCER stem cells (or their progeny, if those are the culprits) which would allow them to be UNIQUELY targetted. We obviously do not want to target all stem cells or we could not repopulate/regenerate/repair all our skin cells, GI cells...in fact almost all the cells in our body except most nervous system cells. But even the brain does have stem cells and can repair to a limited extent.

I don't remember its name, but google their names and the location. If you want to know more, google Max Wicha's name. He has fascinating articles on making "mammospheres" to discover the properties of breast cancer stem cells.

If this theory is right, and I believe it is, it would make sense for all breast cancer patients to have bone marrow biopsies with high-tech methods used to detect isolated tumor cells with the characteristics of stem cells and then follow-up with repeat biopsies to determine if the treatment had the desired consequences. Sounds a lot more satisfactory than just waiting to see if comes back.

This, if it is right, explains why one would want to have the absolute least amount of surgery possible (as any inflammation sends off the stem cells and their division to help "heal" the breach). It remains to be seen what the net-effect of radiation is (decreasing T regulatory cells, making antigen available for education of the immune system, or other unknown effects) and if it is indeed really helpful in this scheme of things.

I like to think about cancer stem cells as similar to mold in the shower. You can TILEX it, bleach it , scrub it, even attack it with ultraviolet light or Lysol, but it just forms thick walled spores and goes into "hibernation" waiting for wet, dark days to occur again in the future so it can multiply again. Even when you think "you got it" there may still be some there waiting for a comeback. We have not yet cured mold (I suffered from an indoor rising river affecting my basement once during El Nino), but perhaps
as more interest, money and lives are at stake we can find those unique properties of breast(and other) stem cells to target.

I really encourage everyone to read the article--and I am depressed today as George Bush is set to veto stem cell research. It is OK to throw them in the trash, noone is prosecuted for that, but not to use them to cure people.

If he cares so much about human life, why did he send more people on death row to the gas chamber/lethal injection than any other governor.
I don't get it!

[Lani]

on the article they list pathways such as Wnt1, sonic hedgehog, etc as being unique to stem cells (unfortunately NOT unique to cancer stem cells, but all stem cells). When I hear about a lecture on these I try to attend, even though they are really technical. When I hear something useful at one of these , I will try to post.

[AlaskaAngel]

Lani, I think you are saying the specimen would have to be fresh from surgery and not a preserved tumor block, right?

I'm nowhere near as sophisticated as Lani, but I also connected with this part of her dialogue:

"If this theory is right, and I believe it is, it would make sense for all breast cancer patients to have bone marrow biopsies with high-tech methods used to detect isolated tumor cells with the characteristics of stem cells and then follow-up with repeat biopsies to determine if the treatment had the desired consequences. Sounds a lot more satisfactory than just waiting to see if comes back."

Here is an article from some time back that came to mind for me:

Micrometastases often persist in breast cancer patients

Reuters Health
Posting Date: March 8, 2005

Last Updated: 2005-03-08 11:27:01 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Despite undergoing surgery and receiving adjuvant therapy, most patients with early-stage breast cancer have bone marrow micrometastases up to 4 years later, according to a report in the March 10th issue of the International Journal of Cancer.

Dr. Martin J. Slade, from Imperial College London, and colleagues used a quantitative PCR (QPCR) technique they developed to look for transcripts of cytokeratin 19, a cancer marker, in the blood and bone marrow of 131 women with breast cancer, most of whom had node-negative T1 disease. These results were compared with standard immunohistochemistry findings.

All of the patients were treated with surgery and adjuvant therapy and had no evidence of metastatic disease on conventional scans.

About half of the patients had QPCR or immunohistochemistry results that indicated bone marrow micrometastases before surgery, the authors note. Of the 91 subjects who had repeat samples taken, 87% and 65% had evidence of metastatic disease at some point with QPCR and immunohistochemistry, respectively.

Systemic adjuvant therapy seemed to have an effect on residual disease. Among patients with residual disease before treatment or at 3 months, 32 of 44 displayed a drop in the CK19/ABL ratio and 15 of 24 showed a drop in cytokeratin-positive cells during follow-up, the authors point out.

"We have demonstrated that in a substantial proportion of patients, minimal residual disease persists using the techniques that we have developed, and that it is possible to monitor patients, preferably using both QPCR and immunohistochemistry, after breast surgery using bone marrow aspirates," the researchers conclude.

Int J Cancer 2005;114:94-100.

[Lani]

there are many ways to process and examine for cells in the bone marrow.

Some just look for markers of epithelial cells (which might be a bit of skin which was carried with the biopsy tool down into the bone at the time of biopsy), others stain for her2, use special hitech optical microscopy etc.

Until they make the type of processing and what/how they are looking for the cells uniform and reproducible, trials looking at serial bone marrow samples
won't mean much.

A team out of Germany headed by Braun has written a lot of papers on the poor prognosis of patients who have tumor cells in their bone marrows by THEIR technique, Chromovision/Clarient has another technique which I believe was being used in clinical trials at UCSF and/or UCLA.

Another work-in-progress for now. I think it might be a way to follow the result of treatment for those treated with adjuvant rather than neoadjuvant therapy, but even in neoadjuvant therapy, if the stem cell theory of breast cancer is correct, the slowly dividing stem cells might not have been affect in the same way the quickly growing tumor cells in the breast were....

Looks like the Senate and the House passed the stem cell bill and now it will be vetoed by George Bush's first veto ever....

[Barbara2]

I had a physical yesterday by my family physician, and we got onto the topic of the oncotype DX test. He had not heard much about it and said he would read up on the topic to see how it works.

He remarked that this type of testing and others like it are the start of a new era in cancer, but he strongly felt that many of the answers we're looking for, lie in stem cell research, and until we are free to use these cells, cancer treatment will be delayed or at least not make the advances that it could, if stem cells could be used. He felt that if stem cells could be used in research, in 20 years time we should be able to individually target cancer for everyone.

My understanding of the biology of these cells is very limited, but I understood him to say that these stem cells could be taken from anyone of us and used for research; [not necessarily from a fetus] which currently is the hot topic. So then what is the big (fetus) debate all about if in fact any stem cell could be used??

Barbara

[mamacze]

Hi Lani
Once again you post a very thought provoking article. I find myself cogitating over this part of your comments:

"I like to think about cancer stem cells as similar to mold in the shower. You can TILEX it, bleach it , scrub it, even attack it with ultraviolet light or Lysol, but it just forms thick walled spores and goes into "hibernation" waiting for wet, dark days to occur again in the future so it can multiply again. Even when you think "you got it" there may still be some there waiting for a comeback.

I am wondering; if we do what we can; ie, "tilex" our cancer cells; but then surround them with an inhospitable niche; ie, incredibly healthy diet; (see RB's postings), if we couldn't then have some control over delaying recurrance of disease.
Thanks again Lani for sharing the fruits of your research labor.
Love,
Kim from CT