Something on Cancer and Stem Cells

Here is a guy (from the NIH, Snuffy's old place) talking about Stem Cells in the context of (the cause of) cancer.

youtube.com/watch?v=-I_quKM...(Not working as expected?)

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check out at 35 minutes in, about docetaxel killing cells that then release il8 as feedback to the stem cells to create replacements. In the graph.

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And wikipedia. The article was stareted in 2005!! Twelve years ago.

en.wikipedia.org/wiki/Cance...

[pjoshea13]

From what I have read in the PCa literature, "stemness" - stem cell-like properties - can be induced in regular PCa cells. It's the ultimate treatment escape path.

Stem-like cells produce telomerase, which makes them "immortal" in terms of cell division. They do not require androgen - they have no AR.

It's a bit misleading to use the term "stem cell", since the prostate contains a small population of prostatic stem cells, whereas the others are PCa cells with stem-like properties.

I had a couple of posts recently where I noted that some PCa drugs delay biochemical recurrence but do not improve overall survival. And yet, it would take forever to bring a drug to market if a clinical trial had to wait until a significant percentage of the participants had died. Targets such as a >50% reduction in PSA seem meaningless if ultimately, there is no survival improvement.

The talk was interesting in that it has been shown in breast cancer, that a particular treatment might shrink a tumor while increasing the population of stem-like cells. Presumably, this can occur in PCa. From the talk it seemed as though he was saying that the stem-like cells were replicating. From the PCa studies, it seems as though cancer cells might be driven into stemness. Whatever. Seems that we need a drug to inhibit the process.

No doubt you will be interested to know that Metformin has anti-CSC properties [1].

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/262...

Prostate Cancer Prostatic Dis. 2015 Dec;18(4):303-9. doi: 10.1038/pcan.2015.35. Epub 2015 Jul 28.

Metformin and prostate cancer stem cells: a novel therapeutic target.

Mayer MJ1,2, Klotz LH1,2, Venkateswaran V1,2.

Author information

Abstract

Prostate cancer is the second most frequently diagnosed cancer in the world. Localized disease can be effectively treated with radiation therapy or radical prostatectomy. However, advanced prostate cancer is more difficult to treat and if metastatic, is incurable. There is a need for more effective therapy for advanced prostate cancer. One potential target is the cancer stem cell (CSC). CSCs have been described in several solid tumors, including prostate cancer, and contribute to therapeutic resistance and tumor recurrence. Metformin, a common oral biguanide used to treat type 2 diabetes, has been demonstrated to have anti-neoplastic effects. Specifically, metformin targets CSCs in breast cancer, pancreatic cancer, glioblastoma and colon cancer. Metformin acts directly on the mitochondria to inhibit oxidative phosphorylation and reduce mitochondrial ATP production. This forces tumor cells to compensate by increasing the rate of glycolysis. CSCs rely heavily on mitochondrial oxidative phosphorylation for energy production. The glycolytic switch results in an energy crisis in these cells. Metformin could be used to exploit this metabolic weakness in CSCs. This would increase CSC sensitivity to conventional cancer therapies, circumventing treatment resistance and enhancing treatment efficacy. This review will explore the characteristics of prostate CSCs, their role in tumor propagation and therapeutic resistance and the role of metformin as a potential prostate CSC sensitizer to current anticancer therapies.

PMID: 26215782 DOI: 10.1038/pcan.2015.35

[Indexed for MEDLINE]

[Hidden in reply to pjoshea13]

arm K of STAMPEDE is trialing metformin.