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Rich66 · 01-22-2010, 04:28 PM

Cancer Stem Cell (CSC) research has accelerated in the last two years

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Cancer Stem Cell (CSC) research has accelerated in the last two years and considerable efforts are now being made to identify drug molecules that selectively target and destroy these cells. (MMD Newswire) January 20, 2010 - The Infoshop by Global Information would like to present a new market research report, " Targeting Cancer Stem Cells: Therapeutic Strategies and Pipeline Developments (2010)" by Biopharm Reports.
This 2010 report gives a comprehensive and up-to-date review of global R&D on CSCs, and strategies to target them. This includes around 40 companies or commercially based research organisations (including 27 SMEs and 8 international pharmaceutical companies) that are progressing drug discovery activities, including drug pipeline (pre-clinical to Phase III), discovery strategy, candidate molecules, drug targets, clinical trials and related areas.
Background: Many cancers contain a subset of stem-like cells believed to play a critical role in the development and progression of the disease. These cells, named Cancer Stem Cells (CSCs), have been found in leukemia, myeloma, breast, prostate, pancreatic, colon, brain, lung and other cancers. Findings suggest that CSCs are able to "seed" new tumour formation and drive metastasis. CSCs also show resistance to a number of chemotherapy drug classes and radiotherapy - which may explain why it is difficult to completely eradicate cancer cells from the body, and why recurrence remains an ever-present threat. If these findings are confirmed in the clinic, the targeting of CSCs alongside the bulk of other cancer cells will offer a new paradigm in cancer therapeutics.
To purchase this report and/or read a full description:
http://www.the-infoshop.com/report/b...stem-cell.html

Clinical Study

British Journal of Cancer (2010) 102, 815–826. doi:10.1038/sj.bjc.6605553 www.bjcancer.com
Published online 9 February 2010
Side-population cells in luminal-type breast cancer have tumour-initiating cell properties, and are regulated by HER2 expression and signalling

T Nakanishi^1,5, S Chumsri¹, N Khakpour¹, A H Brodie¹, B Leyland-Jones², A W Hamburger¹, D D Ross^1,3 and A M Burger⁴

¹Departments of Medicine, Pathology, Pharmacology and Experimental Therapeutics, University of Maryland, School of Medicine, Marlene and Stewart Greenebaum Cancer Center (UMGCC), Baltimore, MD, USA
²Department of Hematology and Medical Oncology, Winship Cancer Center, Emory University, Atlanta, GA, USA
³Baltimore VA Medical Center, Baltimore, MD, USA
⁴Barbara Ann Karmanos Cancer Institute and Department of Pharmacology, Wayne State University, Detroit, MI, USA

Correspondence: Dr AM Burger, Department of Pharmacology, Wayne State University, Hudson-Webber Cancer Research Center, Barbara Ann Karmanos Cancer Institute, Rm 640.2, 4100 John R. Street, Detroit, MI 48201, USA; E-mail: amburger@wayne.edu
⁵Current address: Kanazawa University School of Pharmaceutical Sciences, Kanazawa, Japan.
Received 18 August 2009; Revised 21 December 2009; Accepted 22 December 2009; Published online 9 February 2010.

Top of pageAbstract

Background:

The expression of side-population (SP) cells and their relation to tumour-initiating cells (T-ICs) have been insufficiently studied in breast cancer (BC). We therefore evaluated primary cell cultures derived from patients and a panel of human BC cell lines with luminal- or basal-molecular signatures for the presence of SP and BC stem cell markers.

Methods:

The SPs from luminal-type BC were analysed for BC T-IC characteristics, including human epidermal growth factor receptor 2 (HER2), ERα, IGFBP7 expression and their ability to initiate tumours in non-obese diabetic severe combined immunodeficiency (NOD/SCID) mice. Pharmacological modulators were used to assess the effects of HER2 signalling and breast cancer-resistance protein (BCRP) expression on SPs.

Results:

The SP was more prevalent in the luminal subtype of BC compared with the basal subtype. HER2 expression was significantly correlated with the occurrence of an SP (r²=0.75, P=0.0003). Disappearance of SP in the presence of Ko143, a specific inhibitor of the ATP-binding cassette transporter BCRP, suggests that BCRP is the predominant transporter expressed in this population. The SP also decreased in the presence of HER2 signalling inhibitors AG825 or trastuzumab, strengthening the notion that HER2 contributed to the SP phenotype, likely through downstream AKT signalling. The SP cells from luminal-type MCF-7 cells with enforced expression of HER2, and primary cells with luminal-like properties from a BC patient, displayed enrichment in cells capable of repopulating tumours in NOD/SCID mice. Engraftment of SP cells was inhibited by pretreatment with AG825 or by in vivo treatment with trastuzumab.

Interpretation:

Our findings indicate an important role of HER2 in regulating SP and hence T-ICs in BC, which may account for the poor responsiveness of HER2-positive BCs to chemotherapy, as well as their aggressiveness.

Keywords:

SP, BC, luminal, HER2, T-ICs

01-22-2010, 04:28 PM	#56
Rich66 Senior Member Join Date: Feb 2008 Location: South East Wisconsin Posts: 3,431	Re: Cancer stem cells: The root of all evil? Cancer Stem Cell (CSC) research has accelerated in the last two years E-mail \| Print \| PDF Cancer Stem Cell (CSC) research has accelerated in the last two years and considerable efforts are now being made to identify drug molecules that selectively target and destroy these cells. (MMD Newswire) January 20, 2010 - The Infoshop by Global Information would like to present a new market research report, " Targeting Cancer Stem Cells: Therapeutic Strategies and Pipeline Developments (2010)" by Biopharm Reports. This 2010 report gives a comprehensive and up-to-date review of global R&D on CSCs, and strategies to target them. This includes around 40 companies or commercially based research organisations (including 27 SMEs and 8 international pharmaceutical companies) that are progressing drug discovery activities, including drug pipeline (pre-clinical to Phase III), discovery strategy, candidate molecules, drug targets, clinical trials and related areas. Background: Many cancers contain a subset of stem-like cells believed to play a critical role in the development and progression of the disease. These cells, named Cancer Stem Cells (CSCs), have been found in leukemia, myeloma, breast, prostate, pancreatic, colon, brain, lung and other cancers. Findings suggest that CSCs are able to "seed" new tumour formation and drive metastasis. CSCs also show resistance to a number of chemotherapy drug classes and radiotherapy - which may explain why it is difficult to completely eradicate cancer cells from the body, and why recurrence remains an ever-present threat. If these findings are confirmed in the clinic, the targeting of CSCs alongside the bulk of other cancer cells will offer a new paradigm in cancer therapeutics. To purchase this report and/or read a full description: http://www.the-infoshop.com/report/b...stem-cell.html Clinical Study British Journal of Cancer (2010) 102, 815–826. doi:10.1038/sj.bjc.6605553 www.bjcancer.com Published online 9 February 2010 Side-population cells in luminal-type breast cancer have tumour-initiating cell properties, and are regulated by HER2 expression and signalling T Nakanishi^1,5, S Chumsri¹, N Khakpour¹, A H Brodie¹, B Leyland-Jones², A W Hamburger¹, D D Ross^1,3 and A M Burger⁴ ¹Departments of Medicine, Pathology, Pharmacology and Experimental Therapeutics, University of Maryland, School of Medicine, Marlene and Stewart Greenebaum Cancer Center (UMGCC), Baltimore, MD, USA ²Department of Hematology and Medical Oncology, Winship Cancer Center, Emory University, Atlanta, GA, USA ³Baltimore VA Medical Center, Baltimore, MD, USA ⁴Barbara Ann Karmanos Cancer Institute and Department of Pharmacology, Wayne State University, Detroit, MI, USA Correspondence: Dr AM Burger, Department of Pharmacology, Wayne State University, Hudson-Webber Cancer Research Center, Barbara Ann Karmanos Cancer Institute, Rm 640.2, 4100 John R. Street, Detroit, MI 48201, USA; E-mail: amburger@wayne.edu ⁵Current address: Kanazawa University School of Pharmaceutical Sciences, Kanazawa, Japan. Received 18 August 2009; Revised 21 December 2009; Accepted 22 December 2009; Published online 9 February 2010. Top of pageAbstract Background: The expression of side-population (SP) cells and their relation to tumour-initiating cells (T-ICs) have been insufficiently studied in breast cancer (BC). We therefore evaluated primary cell cultures derived from patients and a panel of human BC cell lines with luminal- or basal-molecular signatures for the presence of SP and BC stem cell markers. Methods: The SPs from luminal-type BC were analysed for BC T-IC characteristics, including human epidermal growth factor receptor 2 (HER2), ERα, IGFBP7 expression and their ability to initiate tumours in non-obese diabetic severe combined immunodeficiency (NOD/SCID) mice. Pharmacological modulators were used to assess the effects of HER2 signalling and breast cancer-resistance protein (BCRP) expression on SPs. Results: The SP was more prevalent in the luminal subtype of BC compared with the basal subtype. HER2 expression was significantly correlated with the occurrence of an SP (r²=0.75, P=0.0003). Disappearance of SP in the presence of Ko143, a specific inhibitor of the ATP-binding cassette transporter BCRP, suggests that BCRP is the predominant transporter expressed in this population. The SP also decreased in the presence of HER2 signalling inhibitors AG825 or trastuzumab, strengthening the notion that HER2 contributed to the SP phenotype, likely through downstream AKT signalling. The SP cells from luminal-type MCF-7 cells with enforced expression of HER2, and primary cells with luminal-like properties from a BC patient, displayed enrichment in cells capable of repopulating tumours in NOD/SCID mice. Engraftment of SP cells was inhibited by pretreatment with AG825 or by in vivo treatment with trastuzumab. Interpretation: Our findings indicate an important role of HER2 in regulating SP and hence T-ICs in BC, which may account for the poor responsiveness of HER2-positive BCs to chemotherapy, as well as their aggressiveness. Keywords: SP, BC, luminal, HER2, T-ICs __________________ Mom's treatment history (link)