Metformin Anticancer Use - Part 1 of 2 - A review of the current evidence - Pre-Publication Proof to appear in Life Sciences, August 2020

[cujoe]

Part One - Anticancer mechanisms of metformin: A review of the current evidence

Parts One is a pre-publication proofs exploring the anticancer effects of metformin. And while it is not specific to PCA, it describe the multitude of ways that metformin affects metabolic and cellular functions of cancer(s). Part Two provides links to recent research for patients thinking of or currently using metformin while taking other PCa SOC medications.

Part One is a relatively brief, but very thorough review of the mechanisms by which metformin has been shown to impact cancer development, growth, and metastases. This is a pre-publication proof, so the excellent graphics and tables are at the very end of the full paper, below the footnoted sources. Also linked at the end of this post are the two cited research papers that are specific to PCa.

Those that know me have heard my spiel about four drivers of PCa. (or as Don Pescado named them, The 4 Horsemen of the PCa Apocalypse). They are cholesterol, glycolysis, inflammation and hormone balance. I note with great interest that metformin has shown the ability to act on all of these except (at least directly) hormone balance. If proven to be the case for PCa, that would make metformin a true 3-fer.

From the paper;

5. Conclusions

This review provides a comprehensive summary of the benefits, consequences and mechanisms of metformin in terms of cancer treatment. The potential antitumor mechanisms of metformin are recognized as one benefit as shown in graphical abstract:

(a) Metformin induces cancer cell growth suppression;

b) Metformin regulates mitochondrial energy metabolism;

(c) Metformin induces epigenetic modification;

(d) Immunoregulatory effects of metformin;

(e) Autophagy effects of metformin;

(f) Anti-angiogenic effects of metformin and other anticancer pathways.

Clinical practice studies are also promising as many of the studies show that metformin may improve survival outcomes. Nevertheless, the clinical data outcomes are preliminary and the results of ongoing trials are eagerly awaited. This review highlights a new avenue for researchers in the application of metformin in cancer treatment and prevention.

6. Limitations and perspectives

Although the emerging roles of metformin in cancer therapy are expanding rapidly and encouraging results have been reported, many questions remained unanswered. There is lack of substantial laboratory evidence and clinical trials assessing the reliability and safety of metformin for the treatment of cancer. In addition, the antitumor mechanisms of metformin are diverse, and the use of metformin may result in unforeseen negative effects in different tumor types. Another concern is that metformin may cause hypoglycemia. An increasing number of evidence indicates that combination of metformin with chemotherapeutic drugs may increase efficacy or overcome drug resistance. Yet, a concurrent use of multiple drugs may sometimes increase toxicity. Moreover, drug combinations are always cost consuming and complex in consideration of pharmaceutical incompatibility compared with monotherapies. Finally, the drug combination might increase the complexity of clinical evaluation. More recently, a study by Stynen [117] showed that metformin may interfere with iron metabolism in yeast cells, and recent work has shown that cancer cells exhibit aberrant iron metabolism [118]. Whether metformin could interfere with iron homeostasis in tumor cells remains unclear. Furthermore, it was recently shown that metformin alters the gut microbiome [119], and there is a possible link between bacterial microbiota and colorectal carcinogenesis [120]. This suggests a potential focus on metformin in the alteration of intestinal flora, as well as the role of intestinal flora in gastrointestinal cancer. Thus, further studies focused on these mechanisms should be conducted.

Anticancer mechanisms of metformin: A review of the current evidence

Abstract link:

doi.org/10.1016/j.lfs.2020....

Full paper link via sci-hub:

sci-hub.tw/10.1016/j.lfs.20...

2 cited research papers that are specific to PCa.

[39] Lee SY, et al. SMILE upregulated by metformin inhibits the function of androgen receptor in prostate cancer cells. Cancer Lett, 2014, 354(2): 390-7

pubmed.ncbi.nlm.nih.gov/251...

[40] Mayer MJ, et al. Metformin and prostate cancer stem cells: a novel therapeutic target. Prostate Cancer Prostatic Dis, 2015,

nature.com/articles/pcan201535

Part Two to follow. Be Safe & Stay Well - Captain K9

[cujoe]

Thanks for your personal input. You and Patrick both go deep into the research for your personal self-directed treatment protocols. That you use every "tool" to do that is a tribute to your scientific intellect and your dedication to finding the best "right path" for each of you to follow. Excellent role models for all cancer patients, regardless of type or stage.

Note that I'm about to edit this post and eliminate Part Two. Turns out once I read through the research paper that was the lead-in for it, there was not much real applicable relevance to PCa. Part Three will now be Part Two of 2. Most of the info in that will be from research many may already be familiar with as it comes from trials that have combined metformin with statins and PCa SOC meds. Some precautions are in order for some combinations.

Looks like the NC monsoons are back next week. Enjoy the better weekend weather while it's here. Stay Well - K9