15 januari 2013: Bron: Cancer Res. 2009 Oct 1;69(19):7507-11. doi: 10.1158/0008-5472.CAN-09-2994. Epub 2009 Sep 14.

Wereldwijd wordt metformin inmiddels in vele studies onderzocht als geneesmiddel tegen verschillende vormen van kanker. Zie ook onder gerelateerde artikelen abstracten van reeds voltooide studies. Waarom metformin wel eens een heel belangrijk medicijn zou kunnen zijn en worden wordt in een studierapport beschreven waarbij muizen werden behandeld met metformin naast chemo. De studie richt zich op wat er gebeurt met stamcellen die kankercellen vormen als muizen die ingespoten zijn met de stamcellen die borstkanker  veroorzaken, behandeld worden met zowel metformin als wel met chemo. Voor leken is dit misschien taaie kost maar voor arten en onderzoekers geeft het volledige studierapport: Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission een uitstekende analyse van het proces dat plaatsvindt bij de muizen die zijn ingespoten met de stamcellen van borstkanker en daarna behandeld met metformin.  

Een ander volledig studierapport Metformin-induced preferential killing of breast cancer initiating CD44+CD24−/low cells is sufficient to overcome primary resistance to trastuzumab in HER2+ human breast cancer xenografts is vorig jaar gepubliceerd over hoe metformin als aanvulling op herceptin - trastuzumab bij Her2-Neu posiitieve borstkanker resistentie tegen herceptin kan doorbreken. Ook een heel interessante studie voor wetenschappers en artsen naar mijn mening. 

Hieronder de abstracten van de studies maar lees ook vooral de gerelateerde artikelen of zoek op metformin in zoekfunctie rechtsbovenaan. Onderaan dit artikel staat ook referentielijst.

Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission

2009 Oct 1;69(19):7507-11. doi: 10.1158/0008-5472.CAN-09-2994. Epub 2009 Sep 14.

Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission.

Source

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School and Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA 02115, USA.

Erratum in

  • Cancer Res. 2009 Nov 15;69(22):8832.

Abstract

The cancer stem cell hypothesis suggests that, unlike most cancer cells within a tumor, cancer stem cells resist chemotherapeutic drugs and can regenerate the various cell types in the tumor, thereby causing relapse of the disease. Thus, drugs that selectively target cancer stem cells offer great promise for cancer treatment, particularly in combination with chemotherapy. Here, we show that low doses of metformin, a standard drug for diabetes, inhibits cellular transformation and selectively kills cancer stem cells in four genetically different types of breast cancer. The combination of metformin and a well-defined chemotherapeutic agent, doxorubicin, kills both cancer stem cells and non-stem cancer cells in culture. Furthermore, this combinatorial therapy reduces tumor mass and prevents relapse much more effectively than either drug alone in a xenograft mouse model. Mice seem to remain tumor-free for at least 2 months after combinatorial therapy with metformin and doxorubicin is ended. These results provide further evidence supporting the cancer stem cell hypothesis, and they provide a rationale and experimental basis for using the combination of metformin and chemotherapeutic drugs to improve treatment of patients with breast (and possibly other) cancers.

PMID:
19752085
[PubMed - indexed for MEDLINE]
PMCID:
PMC2756324
Free PMC Article

Images from this publication.See all images (4) Free text

Figure 1

Metformin-induced preferential killing of breast cancer initiating CD44+CD24−/low cells is sufficient to overcome primary resistance to trastuzumab in HER2+ human breast cancer xenografts

Oncotarget. 2012 April; 3(4): 395–398.
Published online 2012 May 4.
PMCID: PMC3380574

Metformin-induced preferential killing of breast cancer initiating CD44+CD24−/low cells is sufficient to overcome primary resistance to trastuzumab in HER2+ human breast cancer xenografts

Abstract

Trastuzumab-refractory breast cancer stem cells (CSCs) could explain the high rate of primary resistance to single-agent trastuzumab in HER2 gene-amplified breast cancer patients. The identification of agents with strong selective toxicity for trastuzumab-resistant breast CSCs may have tremendous relevance for how HER2+ breast cancer patients should be treated. Using the human breast cancer cell line JIMT-1, which was established from the pleural metastasis of a patient who was clinically resistant to trastuzumab ab initio, we examined whether preferential killing of the putative CD44+CD24 −/low breast CSC population might be sufficient to overcome primary resistance to trastuzumab in vivo. Because recent studies have shown that the anti-diabetic biguanide metformin can exert antitumor effects by targeted killing of CSC-like cells, we explored whether metformin's ability to preferentially kill breast cancer initiating CD44+CD24 −/low cells may have the potential to sensitize JIMT-1 xenograft mouse models to trastuzumab. Upon isolation for breast cancer initiating CD44+CD24 −/low cells by employing magnetic activated cell sorting, we observed the kinetics of metformin-induced killing drastically varied among CSC and non-CSC subpopulations. Metformin's cell killing effect increased dramatically by more than 10-fold in CD44+CD24 −/low breast CSC cells compared to non-CD44+CD24 −/low immunophenotypes. While seven-weeks treatment length with trastuzumab likewise failed to reduce tumor growth of JIMT-1 xenografts, systemic treatment with metformin as single agent resulted in a significant two-fold reduction in tumor volume. When trastuzumab was combined with concurrent metformin, tumor volume decreased sharply by more than four-fold. Given that metformin-induced preferential killing of breast cancer initiating CD44+CD24 −/low subpopulations is sufficient to overcome in vivo primary resistance to trastuzumab, the incorporation of metformin into trastuzumab-based regimens may provide a valuable strategy for treatment of HER2+ breast cancer patients.

REFERENCES

1. Bedard PL, Cardoso F, Piccart-Gebhart MJ. Stemming resistance to HER-2 targeted therapy. J Mammary Gland Biol. 2009;14:55–66.
2. Oliveras-Ferraros C, Vazquez-Martin A, Martin-Castillo B, Cufí S, Del Barco S, Lopez-Bonet E, Brunet J, Menendez JA. Dynamic emergence of the mesenchymal CD44(pos)CD24(neg/low) phenotype in HER2-gene amplified breast cancer cells with de novo resistance to trastuzumab (Herceptin) Biochem Biophys Res Commun. 2010;397:27–33. [PubMed]
3. Fumagalli D, Michiels S, Sotiriou C. CD44+ CD24-/low phenotype and resistance to trastuzumab in HER2-positive breast cancer cell lines. Pharmacogenomics. 2011;12:12–13. [PubMed]
4. Hirsch HA, Iliopoulos D, Tsichlis PN, Struhl K. Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission. Cancer Res. 2009;69:7507–7511. [PMC free article] [PubMed]
5. Vazquez-Martin A, Oliveras-Ferraros C, Del Barco S, Martin-Castillo B, Menendez JA. The anti-diabetic drug metformin suppresses self-renewal and proliferation of trastuzumab-resistant tumor-initiating breast cancer stem cells. Breast Cancer Res Treat. 2011;126:355–364. [PubMed]
6. Iliopoulos D, Hirsch HA, Struhl K. Metformin decreases the dose of chemotherapy for prolonging tumor remission in mouse xenografts involving multiple cancer cell types. Cancer Res. 2011;71:3196–3201. [PMC free article] [PubMed]
7. Tanner M, Kapanen AI, Junttila T, Raheem O, Grenman S, Elo J, Elenius K, Isola J. Characterization of a novel cell line established from a patient with Herceptin-resistant breast cancer. Mol Cancer Ther. 2004;3:1585–1592. [PubMed]
8. Rennstam K, Jönsson G, Tanner M, Bendahl PO, Staaf J, Kapanen AI, Karhu R, Baldetorp B, Borg A, Isola J. Cytogenetic characterization and gene expression profiling of the trastuzumab-resistant breast cancer cell line JIMT-1. Cancer Genet Cytogenet. 2007;172:95–106. [PubMed]
9. Köninki K, Barok M, Tanner M, Staff S, Pitkänen J, Hemmilä P, Ilvesaro J, Isola J. Multiple molecular mechanisms underlying trastuzumab and lapatinib resistance in JIMT-1 breast cancer cells. Cancer Lett. 2010;294:211–219. [PubMed]
10. Oliveras-Ferraros C, Vazquez-Martin A, Martin-Castilló B, Pérez-Martínez MC, Cufí S, Del Barco S, Bernado L, Brunet J, López-Bonet E, Menendez JA. Pathway-focused proteomic signatures in HER2-overexpressing breast cancer with a basal-like phenotype: new insights into de novo resistance to trastuzumab (Herceptin) Int J Oncol. 2010;37:669–678. [PubMed]
11. Martin-Castillo B, Dorca J, Vazquez-Martin A, Oliveras-Ferraros C, Lopez-Bonet E, Garcia M, Del Barco S, Menendez JA. Incorporating the antidiabetic drug metformin in HER2-positive breast cancer treated with neo-adjuvant chemotherapy and trastuzumab: an ongoing clinical-translational research experience at the Catalan Institute of Oncology. Ann Oncol. 2010;21:187–189. [PubMed]

Plaats een reactie ...

Reageer op "Metformin, een veelgebruikt middel bij diabetes 2, blijkt samen met chemo sleutelrol te spelen bij blokkeren van stamcellen die kankercellen vormen."


Gerelateerde artikelen
 

Gerelateerde artikelen

Metformin, een veelgebruikt >> Metformin geeft in vergelijking >> Metformine, een veelgebruikt >> Metformine: Kankerpatiënten >>