Drug Discovery Approaches to Target Wnt Signaling in Cancer Stem Cells
Oncotarget, November, Vol.1, No 7
www.impactjournals.com/oncotarget/
Drug Discovery Approaches to Target Wnt Signaling in Cancer
Stem Cells
Joshua C. Curtin and Matthew V. Lorenzi
1
Oncology Drug Discovery, Research and Development, Bristol-Myers Squibb, Princeton, NJ, USA
Correspondence to: Matthew V. Lorenzi, e-mail: Matthew.Lorenzi@bms.com
Keywords: oncotarget, cancer, stem cells, wnt, drug discovery
Received: August 8, 2010, Accepted: October 27, 2010, Published: October 30, 2010
Copyright: © Curtin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract:
Cancer stem cells (CSCs) represent a unique subset of cells within a tumor that possess self-renewal capacity and pluripotency, and can drive tumor initiation and maintenance. First identified in hematological malignancies, CSCs are now thought to play an important role in a wide variety of solid tumors such as
NSCLC, breast and colorectal cancer. The role of CSCs in driving tumor formation illustrates the dysregulation of differentiation in tumorigenesis. The Wnt, Notch and Hedgehog (HH) pathways are developmental pathways that are commonly activated in many types of cancer. While substantial progress has been made in developing therapeutics targeting Notch and HH, the Wnt pathway has remained an elusive therapeutic target. This review will focus on the clinical relevance of the Wnt pathway in CSCs and tumor cell biology, as well as points of therapeutic intervention and recent advances in targeting Wnt/β-catenin signaling.
Cancer
Stem
Cells:
Hierarchical Model
A
the majority of anti-cancer agents in the clinic. In some cases, these agents are initially very effective at reducing or eliminating tumor burden in the patient. However, tumors often recur, develop
www.impactjournals.com/oncotarget/
Drug Discovery Approaches to Target Wnt Signaling in Cancer
Stem Cells
Joshua C. Curtin and Matthew V. Lorenzi
1
Oncology Drug Discovery, Research and Development, Bristol-Myers Squibb, Princeton, NJ, USA
Correspondence to: Matthew V. Lorenzi, e-mail: Matthew.Lorenzi@bms.com
Keywords: oncotarget, cancer, stem cells, wnt, drug discovery
Received: August 8, 2010, Accepted: October 27, 2010, Published: October 30, 2010
Copyright: © Curtin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract:
Cancer stem cells (CSCs) represent a unique subset of cells within a tumor that possess self-renewal capacity and pluripotency, and can drive tumor initiation and maintenance. First identified in hematological malignancies, CSCs are now thought to play an important role in a wide variety of solid tumors such as
NSCLC, breast and colorectal cancer. The role of CSCs in driving tumor formation illustrates the dysregulation of differentiation in tumorigenesis. The Wnt, Notch and Hedgehog (HH) pathways are developmental pathways that are commonly activated in many types of cancer. While substantial progress has been made in developing therapeutics targeting Notch and HH, the Wnt pathway has remained an elusive therapeutic target. This review will focus on the clinical relevance of the Wnt pathway in CSCs and tumor cell biology, as well as points of therapeutic intervention and recent advances in targeting Wnt/β-catenin signaling.
Cancer
Stem
Cells:
Hierarchical Model
A
the majority of anti-cancer agents in the clinic. In some cases, these agents are initially very effective at reducing or eliminating tumor burden in the patient. However, tumors often recur, develop
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