Hi,
I have heard about the weed analogy of myeloma (e.g you can remove the weed (multiple myeloma cells) but that is temporary unless you remove the root (multiple myeloma stem cell) Thus, there is an urgent need for the development of Multiple Myeloma cancer stem cell-targeted therapies. I have listed a few of them below. My question is how close any of these therapies are to completing clinical trials. Have any of these multiple myeloma CSC-targeted therapies, to your knowledge, stopped myeloma from recurring in humans? If so, are any of them currently available for use?
Myeloma cancer stem cell-targeted therapies:
Rosiglitazone and all-trans retinoic acid
Dimethylaminoparthenolide (DMAPT)
anti-MMSC-1 mAb
Pretransplant targeting of multiple myeloma stem cell (MMSC) with armed activated T cells (aATC)
GRN163L (Imetelstat)
antibody C3B3
MAL3-101
Cyclopamine Rituximab
Interferon + Interleukin-6
What other multiple myeloma CSC-targeted therapies are currently being developed in the pipeline?
Thanks,
A.M.
Forums
Re: Myeloma cancer stem cell-targeted therapies
Myeloma Immunotherapy
http://www.youtube.com/watch?feature=player_embedded&v=RduXfIPWntY
http://www.youtube.com/watch?feature=player_embedded&v=RduXfIPWntY
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suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: Myeloma cancer stem cell-targeted therapies
I probably am going to stir up some strong reactions with this statement, but here goes anyway ...
My understanding is that the myeloma stem cell hypothesis is just that: a hypothesis. There are groups of myeloma specialists, particularly at Johns Hopkins, who believe there really is such a thing as a myeloma stem cell. Yet I'm not sure the theory is broadly accepted throughout the myeloma community.
I say this being well aware of the fact that the Johns Hopkins researchers have published quite a number of papers arguing in favor of the theory. I just don't know if that body of research has been successful in converting most leading myeloma researchers over to the belief that myeloma stem cells exist and are at the root of multiple myeloma.
Perhaps the Beacon could do a survey of myeloma specialists at some point and see how many of them believe the hypothesis is valid. I'd certainly be interested to see the results of such a survey.
My understanding is that the myeloma stem cell hypothesis is just that: a hypothesis. There are groups of myeloma specialists, particularly at Johns Hopkins, who believe there really is such a thing as a myeloma stem cell. Yet I'm not sure the theory is broadly accepted throughout the myeloma community.
I say this being well aware of the fact that the Johns Hopkins researchers have published quite a number of papers arguing in favor of the theory. I just don't know if that body of research has been successful in converting most leading myeloma researchers over to the belief that myeloma stem cells exist and are at the root of multiple myeloma.
Perhaps the Beacon could do a survey of myeloma specialists at some point and see how many of them believe the hypothesis is valid. I'd certainly be interested to see the results of such a survey.
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TerryH
Re: Myeloma cancer stem cell-targeted therapies
Here is an important piece of work on the subject - http://northtexas.myeloma.org/MMSTEMCELL.pdf
This is another very interesting article about targeting the CSC- http://www.nanowerk.com/news/newsid=25338.php
I would be very interested to hear myeloma specialists’ perspectives on the subject -whether they are pro multiple myeloma SC or against it and why. Maybe a survey would be an interesting idea.
This is another very interesting article about targeting the CSC- http://www.nanowerk.com/news/newsid=25338.php
I would be very interested to hear myeloma specialists’ perspectives on the subject -whether they are pro multiple myeloma SC or against it and why. Maybe a survey would be an interesting idea.
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Anonymous
Re: Myeloma cancer stem cell-targeted therapies
I'm sure the researchers who are looking deeper into the possibility that myeloma stem cells exist have looked into this issue, but, as I see it, there is one key weakness to the theory as I understand it.
Namely, that the existence of myeloma stem cells is just one of a number of plausible explanations for the persistence of myeloma after treatment with existing therapies.
For example, just because the treatments we have right now don't kill off all myeloma cells doesn't mean that some kind of "super cell" (stem cell) is responsible for the recurrence of the disease. It could just as easily be that the treatments we currently have do not reach and eradicate all the myeloma cells in the body.
That is, even though the myeloma cells that remain in the body after treatment are essentially the same as those that were killed off, they were in various nooks and crannies of the body that aren't reached with current treatments.
So the persistent cells are not stem cells or some other kind of "super cell". They just happen to have been in the biological equivalent of a bomb shelter when the body was being bombarded with anti-myeloma treatments.
Second -- and this is the more depressing thought -- it could be that myeloma is the result of the body having been permanently altered in some way. Think of the process the body uses to create plasma cells as a kind of assembly line. When it's running correctly, the "assembly line" creates plasma cells that don't have any defects.
Now, if something goes wrong with that assembly line, bad plasma cells will start being created. It's even possible that the "bad" plasma cells could be so bad that they have a tendency to proliferate and cause all sorts of damage to the bones and even neighboring tissue-- i.e., the bad plasma cells could be myeloma cells.
Even if you have a super-dooper anti-myeloma treatment that kills off all the bad plasma cells, you will not have corrected the problem with the body's plasma cell "assembly line". So the body will keep creating the bad plasma cells.
Once again, this happens not because there is some myeloma "stem cell" present in the body. It happens for a totally different reason.
Namely, that the existence of myeloma stem cells is just one of a number of plausible explanations for the persistence of myeloma after treatment with existing therapies.
For example, just because the treatments we have right now don't kill off all myeloma cells doesn't mean that some kind of "super cell" (stem cell) is responsible for the recurrence of the disease. It could just as easily be that the treatments we currently have do not reach and eradicate all the myeloma cells in the body.
That is, even though the myeloma cells that remain in the body after treatment are essentially the same as those that were killed off, they were in various nooks and crannies of the body that aren't reached with current treatments.
So the persistent cells are not stem cells or some other kind of "super cell". They just happen to have been in the biological equivalent of a bomb shelter when the body was being bombarded with anti-myeloma treatments.
Second -- and this is the more depressing thought -- it could be that myeloma is the result of the body having been permanently altered in some way. Think of the process the body uses to create plasma cells as a kind of assembly line. When it's running correctly, the "assembly line" creates plasma cells that don't have any defects.
Now, if something goes wrong with that assembly line, bad plasma cells will start being created. It's even possible that the "bad" plasma cells could be so bad that they have a tendency to proliferate and cause all sorts of damage to the bones and even neighboring tissue-- i.e., the bad plasma cells could be myeloma cells.
Even if you have a super-dooper anti-myeloma treatment that kills off all the bad plasma cells, you will not have corrected the problem with the body's plasma cell "assembly line". So the body will keep creating the bad plasma cells.
Once again, this happens not because there is some myeloma "stem cell" present in the body. It happens for a totally different reason.
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TerryH
Re: Myeloma cancer stem cell-targeted therapies
TerryH,
Here is a piece co-written by well known Myeloma expert Dr. Guido Tricot on the subject from 2011. It gives good insight into this issue.
"One theory, based on the cancer stem cell (CSC) model, is that current multiple myeloma treatments kill the bulk of tumor cells but not the self-renewing multiple myeloma cancer stem cells (MMSCs) subpopulation. The latter type of cells is believed to be the most malignant and drug resistant but also a rare subpopulation of multiple myeloma cells with the ability for self-renewal, division, and maintenance of its undifferentiated state not unlike normal hematopoiets stem cells (HSCs). Although the stem cell phenotype of acute myeloid leukemia has long been identified and is generally accepted, the definitive MMSC phenotype / markers are still being deliberated in the multiple myeloma research community and there are currently several viewpoints on multiple myeloma cells with stemness characteristics. Targeting of MMSCs is clinically relevant since insight into the characteristics of this subpopulation, if it exists, could result in novel therapeutics that can make multiple myeloma a more manageable and even curable disease."
http://www.ajblood.us/files/AJBR1107001.pdf
Mark
Here is a piece co-written by well known Myeloma expert Dr. Guido Tricot on the subject from 2011. It gives good insight into this issue.
"One theory, based on the cancer stem cell (CSC) model, is that current multiple myeloma treatments kill the bulk of tumor cells but not the self-renewing multiple myeloma cancer stem cells (MMSCs) subpopulation. The latter type of cells is believed to be the most malignant and drug resistant but also a rare subpopulation of multiple myeloma cells with the ability for self-renewal, division, and maintenance of its undifferentiated state not unlike normal hematopoiets stem cells (HSCs). Although the stem cell phenotype of acute myeloid leukemia has long been identified and is generally accepted, the definitive MMSC phenotype / markers are still being deliberated in the multiple myeloma research community and there are currently several viewpoints on multiple myeloma cells with stemness characteristics. Targeting of MMSCs is clinically relevant since insight into the characteristics of this subpopulation, if it exists, could result in novel therapeutics that can make multiple myeloma a more manageable and even curable disease."
http://www.ajblood.us/files/AJBR1107001.pdf
Mark
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Mark
Re: Myeloma cancer stem cell-targeted therapies
I cannot speak for the rest of the Beacon Advisors, but the multiple myeloma stem cell (MMSC) or progenitor cell theory remains a hypothesis. There are number of questions that remain unresolved about myeloma progenitor cells -- and, for that matter, all cancer stem cells.
For example: Are these truly stem cells or an induced dedifferentiation akin to the endothelial-mesenchymal transition seen in solid tumors (and more recently demonstrated in myeloma cells as well: Azab Blood 2012). Are these cells truly the harbingers of minimal residual disease - the bane of myeloma therapy? If so can we develop therapies specific for them? Are they involved in myelomagenesis? Are they truly precursors of myeloma cells?
A lot of work, and very nice work, has been published regarding myeloma progenitor cells, but I would suggest that we are neophytes in the unstanding of these cells and their significance to clincal disease presentation, treatment ,and outcomes. As such, whether they are a target for treatment and/or the key to a cure are questions yet to be answered. Today, we are not equipped to directly target these cells clinically. Hopefully, with time we will find the answers and maybe these cells will be one of the keys to long term contol of myeloma.
For example: Are these truly stem cells or an induced dedifferentiation akin to the endothelial-mesenchymal transition seen in solid tumors (and more recently demonstrated in myeloma cells as well: Azab Blood 2012). Are these cells truly the harbingers of minimal residual disease - the bane of myeloma therapy? If so can we develop therapies specific for them? Are they involved in myelomagenesis? Are they truly precursors of myeloma cells?
A lot of work, and very nice work, has been published regarding myeloma progenitor cells, but I would suggest that we are neophytes in the unstanding of these cells and their significance to clincal disease presentation, treatment ,and outcomes. As such, whether they are a target for treatment and/or the key to a cure are questions yet to be answered. Today, we are not equipped to directly target these cells clinically. Hopefully, with time we will find the answers and maybe these cells will be one of the keys to long term contol of myeloma.
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Dr. Ken Shain - Name: Ken Shain, M.D., Ph.D.
Beacon Medical Advisor
Re: Myeloma cancer stem cell-targeted therapies
Hi Dr. Shain,
Thank you for your input on the subject. My thought was that Myeloma CSC-targeted therapies (e.g. GRN163L (Imetelstat), antibody C3B3, MAL3-101) currently target the hypothetical ‘stem cell’ clinically. However, you state that today we are not equipped to directly target these cells clinically.
I also wonder about the root and weed analogy that I have often heard: in order to get rid of myeloma, you must get rid of the 'root,' and not just the 'weed.' Does that mean that those myeloma experts who speak of this analogy believe in the multiple myeloma stem cell theory? If not, what are thery (myeloma experts) refering to in this analogy?
Any clarification would be much appreciated.
Thanks,
A.M.
Thank you for your input on the subject. My thought was that Myeloma CSC-targeted therapies (e.g. GRN163L (Imetelstat), antibody C3B3, MAL3-101) currently target the hypothetical ‘stem cell’ clinically. However, you state that today we are not equipped to directly target these cells clinically.
I also wonder about the root and weed analogy that I have often heard: in order to get rid of myeloma, you must get rid of the 'root,' and not just the 'weed.' Does that mean that those myeloma experts who speak of this analogy believe in the multiple myeloma stem cell theory? If not, what are thery (myeloma experts) refering to in this analogy?
Any clarification would be much appreciated.
Thanks,
A.M.
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A.M.
Re: Myeloma cancer stem cell-targeted therapies
Has anyone ever heard of JQ2?http://www.ted.com/talks/jay_bradner_open_source_cancer_research.html
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RobinMcGowan
14 posts
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