Dr. Weeks’ Comment: We know, and have known for decades, a tremendous amount of cheap and effective strategies to reduce cancer risk including such incontrovertible recommendations such as 1) daily moderate exercise, 2) moderate caloric restriction, 3) lowering night time cortisol levels, 4) lowering fasting blood sugar, 5) lowering fasting insulin levels… – the list goes on! But oncologists don’t typically spend a lot of time encouraging patients in these dietary or lifestyle changes because, well, the nutritionist can handle it and after all the medical doctor should talking about medicines… So why hasn’t your oncologist taught you about a medicine which is cheap, effective and can attack the real culprit in cancer metastasis: the cancer STEM cell? (and also, why do you find, still today in 2011, CANDY in your oncologists waiting room!!!!)
Until Big Pharma can find a way to re-patent the long off-patent drug Metformin (a diabetes drug) for use in cancer, I am afraid your oncologist will have a hard time promoting it. So, in the meanwhile, since your life depends upon it, read the references below and inquire of your primary care practitioner whether she or he will prescribe it for you… OR… you can see a corrective health care practitioner about changing your lifestyle!
“Metformin, the first-line drug for treating diabetes, selectively kills the chemotherapy resistant subpopulation of cancerstem cells (CSC) in genetically distinct types of breast cancer cell lines.”
Drug Resist Updat. 2011 Aug-Oct;14(4-5):212-23. Epub 2011 May 19.
Repositioning chloroquine and metformin to eliminate cancer stem cell traits in pre-malignant lesions.
Unit of Translational Research, Catalan Institute of Oncology-Girona, Avenida de Francia s/n, E-17007 Girona, Catalonia, Spain.
Ideal oncology drugs would be curative after a short treatment course if they could eliminate epithelium-originated carcinomas at their non-invasive, pre-malignant stages. Such ideal molecules, which are expected to molecularly abrogate all the instrumental mechanisms acquired by migrating cancer stem cells (CSCs) to by-pass tumour suppressor barriers, might already exist. We here illustrate how system biology strategies for repositioning existing FDA-approved drugs may accelerate our therapeutic capacity to eliminate CSC traits in pre-invasive intraepithelial neoplasias. First, we describe a signalling network signature that overrides bioenergetics stress- and oncogene-induced senescence (OIS) phenomena in CSCs residing at pre-invasive lesions. Second, we functionally map the anti-malarial chloroquine and the anti-diabetic metformin (“old drugs”) to their recently recognized CSC targets (“new uses”) within the network. By discussing the preclinical efficacy of chloroquine and metformin to inhibiting the genesis and self-renewal of CSCs we finally underscore the expected translational impact of the “old drugs-new uses” repurposing strategy to open a new CSC-targeted chemoprevention era.
Cancer Res. 2011 May 1;71(9):3196-201. Epub 2011 Mar 17.
Metformin decreases the dose of chemotherapy for prolonging tumor remission in mouse xenografts involving multiple cancer cell types.
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
Metformin, the first-line drug for treating diabetes, selectively kills the chemotherapy resistant subpopulation of cancerstem cells (CSC) in genetically distinct types of breast cancer cell lines. In mouse xenografts, injection of metformin and the chemotherapeutic drug doxorubicin near the tumor is more effective than either drug alone in blocking tumor growth and preventing relapse. Here, we show that metformin is equally effective when given orally together with paclitaxel, carboplatin, and doxorubicin, indicating that metformin works together with a variety of standard chemotherapeutic agents. In addition, metformin has comparable effects on tumor regression and preventing relapse when combined with a four-fold reduced dose of doxorubicin that is not effective as a monotherapy. Finally, the combination of metformin and doxorubicin prevents relapse in xenografts generated with prostate and lung cancer cell lines. These observations provide further evidence for the CSC hypothesis for cancer relapse, an experimental rationale for using metformin as part of combinatorial therapy in a variety of clinical settings, and for reducing the chemotherapy dose in cancer patients.
Med Oncol. 2011 Feb 8. [Epub ahead of print]
Department of Medicine, University of Connecticut School of Medicine, Room L2104 MC 1235, 263 Farmington Ave, Farmington, 06103-1235, CT, USA, email@example.com.
Metformin, one of most widely prescribed oral hypoglycemic agents, has recently received increased attention because of its potential antitumorigenic effects that are thought to be independent of its hypoglycemic effects. Several potential mechanisms have been suggested for the ability of metformin to suppress cancer growth in vitro and vivo: (1) activation of LKB1/AMPK pathway, (2) induction of cell cycle arrest and/or apoptosis, (3) inhibition of protein synthesis, (4) reduction in circulating insulin levels, (5) inhibition of the unfolded protein response (UPR), (6) activation of the immune system, and (7) eradication of cancer stem cells. There is also a growing number of evidence, mostly in the form of retrospective clinical studies that suggest that metformin may be associated with a decreased risk of developing cancer and with a better response to chemotherapy. There are currently several ongoing randomized clinical trials that incorporate metformin as an adjuvant to classic chemotherapy and aim to evaluate its potential benefits in this setting. This review highlights basic aspects of the molecular biology of metformin and summarizes new advances in basic science as well as intriguing results from recent clinical studies.
Cell Cycle. 2010 Sep 15;9(18):3807-14. Epub 2010 Sep 25.
Metformin regulates breast cancer stem cell ontogeny by transcriptional regulation of the epithelial-mesenchymal transition (EMT) status.
Catalan Institute of Oncology (ICO), Girona, Catalonia, Spain.
The sole overexpression of pivotal regulators of the embryonic Epithelial-Mesenchymal Transition (EMT) genetic program (“EMT status”) may be sufficient to efficiently drive the ontogeny of the breast cancer stem cell molecular signature independently of changes in EMT functioning (“EMT phenotype”). Using basal-like breast cancer models naturally enriched in either CD44(pos)CD24(low/neg) or CD44(pos)CD24(pos) tumor-initiating cell populations we herein illustrate that non-cytotoxic concentrations of the anti-diabetic drug metformin efficiently impedes the ontogeny of generating the stem cell phenotype by transcriptionally repressing the stem cell property EMT. Metformin treatment dynamically regulated the CD44(pos)CD24 (neg/low) breast cancer stem cell immunophenotype, transcriptionally reprogrammed cells through decreased expression of key drivers of the EMT machinery including the transcription factors ZEB1, TWIST1 and SNAI2 (Slug) and the pleiotrophic cytokines TGFÎ²s, and lastly impeded the propensity of breast cancer stem cells to form multicellular “microtumors” in non-adherent and non-differentiating conditions (i.e., “mammospheres”). These findings, altogether, provide strong motivation for the continued molecular understanding and clinical development of metformin as a non-toxic therapeutic aimed to interdict the breast cancer stem cell phenotype by targeting EMT, a molecular process that is central to the ontogenesis of the breast cancer stem cell molecular signature.