Metformin Decreases the Dose of Chemotherapy for Prolonging Tumor Remission in Mouse Xenografts Involving Multiple Cancer Cell Types
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TLDR
It is shown that met formin is equally effective when given orally together with paclitaxel, carboplatin, and doxorubicin, indicating that metformin works together with a variety of standard chemotherapeutic agents.Abstract:
Metformin, the first-line drug for treating diabetes, selectively kills the chemotherapy-resistant, sub-population of cancer stem cells 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 metformin combined with a 4-fold reduced dose of doxorubicin that is not effective as a monotherapy. Lastly, 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 cancer stem cell hypothesis for cancer relapse, as well as 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.read more
Citations
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Metformin—mode of action and clinical implications for diabetes and cancer
Ida Pernicova,Márta Korbonits +1 more
TL;DR: The updated understanding of the antigluconeogenic action of met formin in the liver and the implications of the discoveries of metformin targets for the treatment of diabetes mellitus and cancer are discussed.
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To differentiate or not — routes towards metastasis
TL;DR: Two principle types of metastatic progression are proposed: phenotypic plasticity involving transient EMT–MET processes and intrinsic genetic alterations keeping cells in an EMT and stemness state.
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Investigating Metformin for Cancer Prevention and Treatment: The End of the Beginning
TL;DR: There are tantalizing clues that justify the investigation of antineoplastic activities of biguanides, but the complexity of their biologic effects requires further translational research to guide clinical trial design.
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Metformin inhibits the inflammatory response associated with cellular transformation and cancer stem cell growth
TL;DR: Observations suggest that metformin inhibits a signal transduction pathway that results in an inflammatory response that stimulates the inflammatory pathway associated with a wide variety of cancers.
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Metformin in Cancer Treatment and Prevention
TL;DR: The link between metformin and cancer, the potential for met formin in oncology, and limitations of currently available evidence are outlined.
References
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Molecular Definition of Breast Tumor Heterogeneity
Michail Shipitsin,Lauren L. Campbell,Pedram Argani,Stanislawa Weremowicz,Noga Bloushtain-Qimron,Jun Yao,Tatiana Nikolskaya,Tatiana Serebryiskaya,Rameen Beroukhim,Min Hu,Marc K. Halushka,Saraswati Sukumar,Leroy M. Parker,Karen S. Anderson,Lyndsay Harris,Judy Garber,Andrea L. Richardson,Stuart J. Schnitt,Yuri Nikolsky,Rebecca Gelman,Kornelia Polyak +20 more
TL;DR: In this paper, gene expression and genetic profiles of cells purified from cancerous and normal breast tissue using markers previously associated with stem-cell-like properties were determined using markers from the TGF-β pathway, where its inhibition induced a more epithelial phenotype.
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An Epigenetic Switch Involving NF-κB, Lin28, Let-7 MicroRNA, and IL6 Links Inflammation to Cell Transformation
TL;DR: It is shown that transient activation of Src oncoprotein can mediate an epigenetic switch from immortalized breast cells to a stably transformed line that forms self-renewing mammospheres that contain cancer stem cells.
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Downregulation of miRNA-200c Links Breast Cancer Stem Cells with Normal Stem Cells
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TL;DR: The coordinated downregulation of three microRNA clusters and the similar functional regulation of clonal expansion by miR-200c provide a molecular link that connects BCSCs with normal stem cells.