Home LiteratureArticle Details
PMID: 24975284 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

Safely targeting cancer stem cells via selective catenin coactivator antagonism.

Cancer science ·Vol. 105 ·No. 9 ·2014-09-00 ·Pages 1087-92

Lenz HJ, Kahn M

Abstract

Throughout our life, long-lived somatic stem cells (SSC) regenerate adult tissues both during homeostatic processes and repair after injury. The role of aberrant regulation of SSC has also recently gained prominence in the field of cancer research. Following malignant transformation, so termed cancer stem cells (CSC), endowed with the same properties as SSC (i.e. the ability to both self-renew and generate differentiated progenitors), play a major part in tumor initiation, therapy resistance and ultimately relapse. The same signaling pathways involved in regulating SSC maintenance are involved in the regulation of CSC. CSC exist in a wide array of tumor types, including leukemias, and brain, breast, prostate and colon tumors. Consequently, one of the key goals in cancer research over the past decade has been to develop therapeutic strategies to safely eliminate the CSC population without damaging the endogenous SSC population. A major hurdle to this goal lies in the identification of the key mechanisms that distinguish CSC from the normal endogenous tissue stem cells. This review will discuss the discovery of the specific CBP/catenin antagonist ICG-001 and the ongoing clinical development of the second generation CBP/catenin antagonist PRI-724. Importantly, specific CBP/catenin antagonists appear to have the ability to safely eliminate CSC by taking advantage of an intrinsic differential preference in the way SSC and CSC divide.

Keywords
Asymmetric CREB-binding protein Wnt/catenin p300 symmetric
MeSH Terms
Animals Antineoplastic Agents/pharmacology Bridged Bicyclo Compounds, Heterocyclic/pharmacology Catenins/antagonists & inhibitors Gene Expression Regulation, Neoplastic Humans Neoplasms/drug therapy,pathology Neoplastic Stem Cells/drug effects,metabolism Peptide Fragments/antagonists & inhibitors,metabolism Pyrimidinones/pharmacology Sialoglycoproteins/antagonists & inhibitors,metabolism Wnt Signaling Pathway
Chemicals
Antineoplastic Agents Bridged Bicyclo Compounds, Heterocyclic Catenins ICG 001 Peptide Fragments Pyrimidinones Sialoglycoproteins bone sialoprotein (35-62), human
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Lenz Heinz-Josef
USC Norris Comprehensive Cancer Center, USC Center for Molecular Pathways and Drug Discovery, University of Southern California, Los Angeles, California, USA.
Kahn Michael
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Article Info
Journal
Cancer science
Abbr.
Cancer Sci
ISSN
1349-7006
DOI
10.1111/cas.12471
Published
2014-09-00
Epub
2014-00-06
Pages
1087-92
Language
English
Region
England
NLM ID
101168776
PMCID
PMC4175086
Subset
IM
Grants
NCI NIH HHS · R01 CA166161 · United States
NHLBI NIH HHS · 1R01 HL112638-01 · United States
NCI NIH HHS · 1R01CA166161-01A1 · United States
NIAID NIH HHS · 1R21AI105057-01 · United States
NCI NIH HHS · P30 CA014089 · United States
NINDS NIH HHS · 1R21NS074392-01 · United States
External Links
PubMed source DOI: 10.1111/cas.12471 PMC Full Text View journal details
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