"VSports在线直播" Self-renewal as a therapeutic target in human colorectal cancer

Antonija Kreso¹, Peter van Galen², Nicholas M Pedley³, Evelyne Lima-Fernandes⁴, Catherine Frelin⁵, Thomas Davis⁶, Liangxian Cao⁶, Ramil Baiazitov⁶, Wu Du⁶, Nadiya Sydorenko⁶, Young-Choon Moon⁶, Lianne Gibson³, Yadong Wang³, Cherry Leung³, Norman N Iscove⁷, Cheryl H Arrowsmith⁸, Eva Szentgyorgyi⁹, Steven Gallinger¹⁰, John E Dick¹¹, Catherine A O'Brien¹²

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¹ 1] Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [2] Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
² Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
³ 1] Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [2] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
⁴ Structural Genomics Consortium, Toronto, Ontario, Canada.
⁵ 1] Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [2] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
⁶ PTC Therapeutics, South Plainfield, New Jersey, USA.
⁷ 1] Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [2] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. [3] Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
⁸ 1] Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [2] Structural Genomics Consortium, Toronto, Ontario, Canada. [3] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
⁹ Department of Pathology, Toronto General Hospital, Toronto, Ontario, Canada.
¹⁰ 1] Department of Surgery, Toronto General Hospital, Toronto, Ontario, Canada. [2] Fred Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
¹¹ 1] Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [2] Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. [3].
¹² 1] Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [2] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. [3] Department of Surgery, Toronto General Hospital, Toronto, Ontario, Canada. [4].

PMID: 24292392
DOI: "VSports注册入口" 10.1038/nm.3418

Self-renewal as a therapeutic target in human colorectal cancer

Antonija Kreso et al. Nat Med. 2014 Jan.

. 2014 Jan;20(1):29-36.

doi: 10.1038/nm.3418. Epub 2013 Dec 1.

Authors

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¹ 1] Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [2] Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
² Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
³ 1] Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [2] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
⁴ Structural Genomics Consortium, Toronto, Ontario, Canada.
⁵ 1] Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [2] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
⁶ PTC Therapeutics, South Plainfield, New Jersey, USA.
⁷ 1] Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [2] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. [3] Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
⁸ 1] Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [2] Structural Genomics Consortium, Toronto, Ontario, Canada. [3] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
⁹ Department of Pathology, Toronto General Hospital, Toronto, Ontario, Canada.
¹⁰ 1] Department of Surgery, Toronto General Hospital, Toronto, Ontario, Canada. [2] Fred Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
¹¹ 1] Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [2] Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. [3].
¹² 1] Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [2] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. [3] Department of Surgery, Toronto General Hospital, Toronto, Ontario, Canada. [4].

PMID: 24292392
DOI: 10.1038/nm.3418

Abstract

Tumor recurrence following treatment remains a major clinical challenge. Evidence from xenograft models and human trials indicates selective enrichment of cancer-initiating cells (CICs) in tumors that survive therapy. Together with recent reports showing that CIC gene signatures influence patient survival, these studies predict that targeting self-renewal, the key 'stemness' property unique to CICs, may represent a new paradigm in cancer therapy. Here we demonstrate that tumor formation and, more specifically, human colorectal CIC function are dependent on the canonical self-renewal regulator BMI-1. Downregulation of BMI-1 inhibits the ability of colorectal CICs to self-renew, resulting in the abrogation of their tumorigenic potential. Treatment of primary colorectal cancer xenografts with a small-molecule BMI-1 inhibitor resulted in colorectal CIC loss with long-term and irreversible impairment of tumor growth. Targeting the BMI-1-related self-renewal machinery provides the basis for a new therapeutic approach in the treatment of colorectal cancer. VSports手机版.

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"V体育官网入口" Colorectal cancer: targeting self-renewal of cancer stem cells in colorectal cancer-a future treatment option?
Leake I. Leake I. Nat Rev Gastroenterol Hepatol. 2014 Feb;11(2):75. doi: 10.1038/nrgastro.2013.252. Epub 2013 Dec 17. Nat Rev Gastroenterol Hepatol. 2014. PMID: 24345889 No abstract available.
"VSports app下载" Targeting self-renewal, an Achilles' heel of cancer stem cells.
Wicha MS. Wicha MS. Nat Med. 2014 Jan;20(1):14-5. doi: 10.1038/nm.3434. Nat Med. 2014. PMID: 24398956 No abstract available.
Anticancer drugs: Curbing self-renewal of cancer-initiating cells.
Crunkhorn S. Crunkhorn S. Nat Rev Drug Discov. 2014 Feb;13(2):102. doi: 10.1038/nrd4237. Nat Rev Drug Discov. 2014. PMID: 24481304 No abstract available.

References

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1. J Cancer Res Clin Oncol. 2010 Jul;136(7):997-1006 - PubMed
1. J Natl Cancer Inst. 2008 May 7;100(9):672-9 - PubMed
1. Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8 - PubMed
1. Cell Stem Cell. 2010 Sep 3;7(3):299-313 - PubMed (V体育官网入口)

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