I found this article (see below) on the research into using common antibiotics to kill cancer stem cells in some of the most common types of cancers. The research was done in vitro and did not use any blood cancer cell lines. At the end of the article though they discuss the results of other trials with doxycycline with the following quote:
“Interestingly, it was noted that even lymphoma patients that were “bacteria-free” benefited from only a 3-week course of doxycycline therapy, and showed complete remission of the disease”.
I have to wonder if antibiotics could be effective against myeloma stem cells, especially as to the best of my knowledge the existing treatments for myeloma not believed to target myeloma stem cells.
Also interesting is the bone marrow toxicity of the antibiotic chloramphenicol. I think this is not an antibiotic that someone with myeloma would want to use. I will have to keep this in mind when I go to urgent care and get prescribed antibiotics. I am not sure the average GP would catch this.
R Lamb et al, "Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: Treating cancer like an infectious disease," Oncotarget, Jan 2015 (full text of article)
Abstract:
Here, we propose a new strategy for the treatment of early cancerous lesions and advanced metastatic disease, via the selective targeting of cancer stem cells (CSCs), a.k.a., tumor-initiating cells (TICs). We searched for a global phenotypic characteristic that was highly conserved among cancer stem cells, across multiple tumor types, to provide a mutation-independent approach to cancer therapy. This would allow us to target cancer stem cells, effectively treating cancer as a single disease of “stemness”, independently of the tumor tissue type.
Using this approach, we identified a conserved phenotypic weak point – a strict dependence on mitochondrial biogenesis for the clonal expansion and survival of cancer stem cells. Interestingly, several classes of FDA-approved antibiotics inhibit mitochondrial biogenesis as a known “side-effect”, which could be harnessed instead as a “therapeutic effect”.
Based on this analysis, we now show that 4-to-5 different classes of FDA-approved drugs can be used to eradicate cancer stem cells, in 12 different cancer cell lines, across 8 different tumor types (breast, DCIS, ovarian, prostate, lung, pancreatic, melanoma, and glioblastoma (brain)). These five classes of mitochondrially-targeted antibiotics include: the erythromycins, the tetracyclines, the glycylcyclines, an anti-parasitic drug, and chloramphenicol. Functional data are presented for one antibiotic in each drug class: azithromycin, doxycycline, tigecycline, pyrvinium pamoate, as well as chloramphenicol, as proof-of-concept. Importantly, many of these drugs are non-toxic for normal cells, likely reducing the side effects of anti-cancer therapy.
Thus, we now propose to treat cancer like an infectious disease, by repurposing FDA-approved antibiotics for anti-cancer therapy, across multiple tumor types. These drug classes should also be considered for prevention studies, specifically focused on the prevention of tumor recurrence and distant metastasis.
Finally, recent clinical trials with doxycycline and azithromycin (intended to target cancer-associated infections, but not cancer cells) have already shown positive therapeutic effects in cancer patients, although their ability to eradicate cancer stem cells was not yet appreciated.
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Re: Antibiotics to kill cancer stem cells
This article is great! I'm concerned though that we all read so many of these papers that hold promising information that never seems to play out. I wish there was some way for us as patients to push these things into clinical trials ASAP!!
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blair77 - Who do you know with myeloma?: My husband
- When were you/they diagnosed?: April 2013
- Age at diagnosis: 43
Re: Antibiotics to kill cancer stem cells
At the end of the article this discusses some clinical trials that are going on now. Let’s hope they are successful. It seems that this could be applicable to more cancers than the researchers were able to investigate with the resources they had.
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Eric Hofacket - Name: Eric H
- When were you/they diagnosed?: 01 April 2011
- Age at diagnosis: 44
Re: Antibiotics to kill cancer stem cells
For folks new to the forum and multiple myeloma, doxil (which is a derivative of doxycycline) has been used by multiple myeloma specialists in both front line and relapsed settings for a number of years. As I understand it, the exact mechanism for why it works in multiple myeloma isn't fully understood. It's exciting to hear about drugs like doxycline being able to target the disease at the stem cell level.
If I progress to symptomatic multiple myeloma, one of my specialists is likely considering the combo of Velcade, pegylated doxil and low-dose dex (aka VDd or PAd) for my initial treatment.
If I progress to symptomatic multiple myeloma, one of my specialists is likely considering the combo of Velcade, pegylated doxil and low-dose dex (aka VDd or PAd) for my initial treatment.
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Antibiotics to kill cancer stem cells
Thanks for the update Billy. I recall reading something about antibiotics and myeloma before but did not recall where or what the details were. You memory recall is a lot better than mine. What I found interesting in this article is for the cancers they investigated is they believe the mechanism of action is on the mitochondria of the cancer stem cells. The evolutionary history of mitochondria and the close relation to bacteria was also interesting. I wonder if this is the same mechanism of action in the clinical trials you cited which would add the understanding of how doxycycline is effective against myeloma. I am also interested in the targeting of cancer stem cells aspect. What else is there that does this? If this is true for myeloma then it may make sense to add it to many if not all the drug therapy combinations.
Another take away I have from this is for people with myeloma and compromised immune systems who are in urgent care frequently getting treated with antibiotics for infections, should there be some consideration that some antibiotics may be a better choice for us that others? Would we be the ones who would have to bring that knowledge? Should the oncologist get involved with antibiotic selection for routine infections?
Another take away I have from this is for people with myeloma and compromised immune systems who are in urgent care frequently getting treated with antibiotics for infections, should there be some consideration that some antibiotics may be a better choice for us that others? Would we be the ones who would have to bring that knowledge? Should the oncologist get involved with antibiotic selection for routine infections?
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Eric Hofacket - Name: Eric H
- When were you/they diagnosed?: 01 April 2011
- Age at diagnosis: 44
Re: Antibiotics to kill cancer stem cells
Just a little observation from my research. Dr. Durie posted a paper in the 90's that Biaxin (clarithromycin) is active against multiple myeloma. Not sure if it's active by itself or it just synergizes other drugs (novel agents).
If you go through all of the ASH presentations, or search them, you will see a few trials using Biaxin as part of the mix.
If you go through all of the ASH presentations, or search them, you will see a few trials using Biaxin as part of the mix.
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JPC - Name: JPC
Re: Antibiotics to kill cancer stem cells
Hi Multibilly,
Where did you see that Doxil is a derivative of doxycycline? Doxil is an encapsulated form of doxorubicin (Adriamycin). Doxil is considered an anthracycline antibiotic used to treat cancer. Doxycycline is a tetracycline antibiotic typically used to treat acne and rosacea (skin rash). As someone who used both Doxil and doxycycline since being diagnosed with myeloma, I can tell you the side effect profile is quite different!
I am going to get a good laugh about this with my doctor next time I see her. I needed doxycycline due to a skin rash after my allo. Who needs the immunotherapy of a healthy functioning donor immune system to cure patients of blood cancer when different antibiotics might do the trick?!?
Mark
"For folks new to the forum and multiple myeloma, doxil (which is a derivative of doxycycline) has been used by multiple myeloma specialists in both front line and relapsed settings for a number of years."
Where did you see that Doxil is a derivative of doxycycline? Doxil is an encapsulated form of doxorubicin (Adriamycin). Doxil is considered an anthracycline antibiotic used to treat cancer. Doxycycline is a tetracycline antibiotic typically used to treat acne and rosacea (skin rash). As someone who used both Doxil and doxycycline since being diagnosed with myeloma, I can tell you the side effect profile is quite different!
I am going to get a good laugh about this with my doctor next time I see her. I needed doxycycline due to a skin rash after my allo. Who needs the immunotherapy of a healthy functioning donor immune system to cure patients of blood cancer when different antibiotics might do the trick?!?
Mark
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Mark11
Re: Antibiotics to kill cancer stem cells
Yes, they are quite different drugs and my statement wrt being a derivative was indeed incorrect. Enjoy the laughter at your doctor's office.
For any one interested in comparing the two molecules:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC127468/figure/f1/
For any one interested in comparing the two molecules:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC127468/figure/f1/
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
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