Some of you may already have seen this news, but I thought it might be worth sharing here just in case.
To summarize the news: An older drug called thioridazine, which was used to treat schizophrenia and psychosis, has been shown in laboratory studies to destroy cancer stem cells. A number of other existing drugs with a similar effect also were identified during the same research. There are plans to test thioridazine in patients with acute myeloid leukemia.
Below is the press release from McMaster University in Canada about the study, and at the end of the posting is the abstract for the research paper.
PRESS RELEASE:
McMaster University researchers discover drug destroys human cancer stem cells but not healthy ones
Published: May 24, 2012
A team of scientists at McMaster University has discovered a drug, thioridazine, successfully kills cancer stem cells in the human while avoiding the toxic side-effects of conventional cancer treatments.
"The unusual aspect of our finding is the way this human-ready drug actually kills cancer stem cells; by changing them into cells that are non-cancerous," said Mick Bhatia, the principal investigator for the study and scientific director of McMaster's Stem Cell and Cancer Research Institute (SCC-RI) in the Michael G. DeGroote School of Medicine.
Unlike chemotherapy and radiation, thioridazine appears to have no effect on normal stem cells.
The research, published today in the science journal CELL, holds the promise of a new strategy and discovery pipeline for the development of anticancer drugs in the treatment of various cancers. The research team has identified another dozen drugs that have good potential for the same response.
For 15 years, some researchers have believed stem cells are the source of many cancers. In 1997, Canadian researchers first identified cancer stem cells in certain types of leukemia. Cancer stem cells have since been identified in blood, breast, brain, lung, gastrointestinal, prostate and ovarian cancer.
To test more than a dozen different compounds, McMaster researchers pioneered a fully automated robotic system to identify several drugs, including thioridazine.
"Now we can test thousands of compounds, eventually defining a candidate drug that has little effect on normal stem cells but kills the cells that start the tumor," said Bhatia.
The next step is to test thioridazine in clinical trials, focusing on patients with acute myeloid leukemia whose disease has relapsed after chemotherapy. Bhatia wants to find out if the drug can put their cancer into remission, and by targeting the root of the cancer (cancer stem cells) prevent the cancer from coming back. Researchers at McMaster have already designed how these trials would be done.
Bhatia's team found thioridazine works through the dopamine receptor on the surface of the cancer cells in both leukemia and breast cancer patients. This means it may be possible to use it as a biomarker that would allow early detection and treatment of breast cancer and early signs of leukemia progression, he said. The research team's next step is to investigate the effectiveness of the drug in other types of cancer. In addition, the team will explore several drugs identified along with thioridazine. In the future, thousands of other compounds will be analyzed with McMaster robotic stem cell screening system in partnership with collaborations that include academic groups as well as industry.
"The goal for all of the partners is the same — to find unique drugs to change the way we tackle and treat cancer," he said.
ABSTRACT:
Cell. 2012 May 23. [Epub ahead of print]
Identification of Drugs Including a Dopamine Receptor Antagonist that Selectively Target Cancer Stem Cells.
Sachlos E, Risueño RM, Laronde S, Shapovalova Z, Lee JH, Russell J, Malig M, McNicol JD, Fiebig-Comyn A, Graham M, Levadoux-Martin M, Lee JB, Giacomelli AO, Hassell JA, Fischer-Russell D, Trus MR, Foley R, Leber B, Xenocostas A, Brown ED, Collins TJ, Bhatia M.
Source: McMaster Stem Cell and Cancer Research Institute, Faculty of Health Sciences, McMaster University, 1280 Main Street West, MDCL 5029, Hamilton, ON L8S4L8, Canada.
Abstract: Selective targeting of cancer stem cells (CSCs) offers promise for a new generation of therapeutics. However, assays for both human CSCs and normal stem cells that are amenable to robust biological screens are limited. Using a discovery platform that reveals differences between neoplastic and normal human pluripotent stem cells (hPSC), we identify small molecules from libraries of known compounds that induce differentiation to overcome neoplastic self-renewal. Surprisingly, thioridazine, an antipsychotic drug, selectively targets the neoplastic cells, and impairs human somatic CSCs capable of in vivo leukemic disease initiation while having no effect on normal blood SCs. The drug antagonizes dopamine receptors that are expressed on CSCs and on breast cancer cells as well. These results suggest that dopamine receptors may serve as a biomarker for diverse malignancies, demonstrate the utility of using neoplastic hPSCs for identifying CSC-targeting drugs, and provide support for the use of differentiation as a therapeutic strategy.
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Re: Thioridazine and cancer stem cells
Hi Terry, That sounds really interesting. Let's hope that the thioridazine can put the patients with myeloid leukaemia back into a remission. I wonder how the doses used in the trial would compare with the dose given for psychiatric disorders? i.e. I guess the doses would also be adjusted for safety and efficiency, like anything else in pharmacy research studies. In the last week, there has been a 'thread' about the possibility of there being specific stem cells just for myeloma (gloomy thought). This article seems to indicate that there are stem cells specific to certain other cancers too! So of course if there were a drug that could deal with that problem, it would be a new wonder drug. Hope you will keep an eye out for the results of that clinical trial, since I know you are perusing the literature a lot.
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Nancy Shamanna - Name: Nancy Shamanna
- Who do you know with myeloma?: Self and others too
- When were you/they diagnosed?: July 2009
Re: Thioridazine and cancer stem cells
Nancy,
The info available states that the dosage of Thioridazine required for treating cancer is half the mean therapeutic adult dosage for schizophrenia, ~ 50mg to 100mg, three times daily, not to exceed 800mg per day. This means that you should expect that 50mg, three times daily for ten to twenty days would be sufficient, although no practical harm would come from 100mg. Tumors typically decrease in size by half within 24 hours, and are undetectable within ten days. Recurrence is not possible, since the cancer stem cells also no longer exist. In the 1960's, studies have reported on the mysterious fact that inpatients confined to mental institutions (willingly and not) had a cancer rate of only 1/10th that of the general population. And that was attributed to the fact that 10% of the patients were not prescribed Thioridazine.
Thioridazine works by suppressing the electromagnetic cell signals (which is how MRI's work) from the cancer cells as well as the cancer stem cells, leaving their DNA vulnerable to invasion from surrounding signals. This is how they revert to "normal" and are able to commit suicide like normal cells. The concerns about cardiac arrhythmia related to Thioridazine use are only relevant over long-term usage (several years).
The info available states that the dosage of Thioridazine required for treating cancer is half the mean therapeutic adult dosage for schizophrenia, ~ 50mg to 100mg, three times daily, not to exceed 800mg per day. This means that you should expect that 50mg, three times daily for ten to twenty days would be sufficient, although no practical harm would come from 100mg. Tumors typically decrease in size by half within 24 hours, and are undetectable within ten days. Recurrence is not possible, since the cancer stem cells also no longer exist. In the 1960's, studies have reported on the mysterious fact that inpatients confined to mental institutions (willingly and not) had a cancer rate of only 1/10th that of the general population. And that was attributed to the fact that 10% of the patients were not prescribed Thioridazine.
Thioridazine works by suppressing the electromagnetic cell signals (which is how MRI's work) from the cancer cells as well as the cancer stem cells, leaving their DNA vulnerable to invasion from surrounding signals. This is how they revert to "normal" and are able to commit suicide like normal cells. The concerns about cardiac arrhythmia related to Thioridazine use are only relevant over long-term usage (several years).
Re: Thioridazine and cancer stem cells
Thanks for the info, O'Bagel!
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Nancy Shamanna - Name: Nancy Shamanna
- Who do you know with myeloma?: Self and others too
- When were you/they diagnosed?: July 2009
Re: Thioridazine and cancer stem cells
I was thinking maybe they could add Thioridazine to harvested stem cells outside the body in really high concentrations to kill the cancer stem cells before doing the transplant but the post above suggest this may not have any effect. The cancer cells may need to be in the body to respond to signals from other cells to die. Good news though, yet another drug in the arsenal against multiple myeloma.
Would a clinical trial or FDA approval really be needed for a doctor to start using this already approved drug? If it is cheap and no other drugs are working, what is there to lose? We may be be able to learn very quickly how effective it is as a treatment, but given myeloma's tendency to always come back even after CR for years with no detectable signs of disease, we may have to wait for many years before learning it is a potential cure. I suppose that is the problem with determining if any drug is a cure for myeloma, it may be a long wait and see.
Would a clinical trial or FDA approval really be needed for a doctor to start using this already approved drug? If it is cheap and no other drugs are working, what is there to lose? We may be be able to learn very quickly how effective it is as a treatment, but given myeloma's tendency to always come back even after CR for years with no detectable signs of disease, we may have to wait for many years before learning it is a potential cure. I suppose that is the problem with determining if any drug is a cure for myeloma, it may be a long wait and see.
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Eric Hofacket - Name: Eric H
- When were you/they diagnosed?: 01 April 2011
- Age at diagnosis: 44
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