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PMID: 17979879 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Review

Recent advances in cancer stem/progenitor cell research: therapeutic implications for overcoming resistance to the most aggressive cancers.

Journal of cellular and molecular medicine ·Vol. 11 ·No. 5 ·2007-00-00 ·Pages 981-1011

Mimeault M, Hauke R, Mehta PP, Batra SK

Abstract

Overcoming intrinsic and acquired resistance of cancer stem/progenitor cells to current clinical treatments represents a major challenge in treating and curing the most aggressive and metastatic cancers. This review summarizes recent advances in our understanding of the cellular origin and molecular mechanisms at the basis of cancer initiation and progression as well as the heterogeneity of cancers arising from the malignant transformation of adult stem/progenitor cells. We describe the critical functions provided by several growth factor cascades, including epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), stem cell factor (SCF) receptor (KIT), hedgehog and Wnt/beta-catenin signalling pathways that are frequently activated in cancer progenitor cells and are involved in their sustained growth, survival, invasion and drug resistance. Of therapeutic interest, we also discuss recent progress in the development of new drug combinations to treat the highly aggressive and metastatic cancers including refractory/relapsed leukaemias, melanoma and head and neck, brain, lung, breast, ovary, prostate, pancreas and gastrointestinal cancers which remain incurable in the clinics. The emphasis is on new therapeutic strategies consisting of molecular targeting of distinct oncogenic signalling elements activated in the cancer progenitor cells and their local microenvironment during cancer progression. These new targeted therapies should improve the efficacy of current therapeutic treatments against aggressive cancers, and thereby preventing disease relapse and enhancing patient survival.

MeSH Terms
Animals Disease Progression Drug Resistance, Neoplasm Humans Neoplasms/classification,pathology,therapy Neoplastic Stem Cells/pathology
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Mimeault M
Department of Biochemistry and Molecular Biology, Eppley Institute of Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA. mmimeault@unmc.edu
Hauke R
Mehta P P
Batra S K
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Article Info
Journal
Journal of cellular and molecular medicine
Abbr.
J Cell Mol Med
ISSN
1582-1838
DOI
10.1111/j.1582-4934.2007.00088.x
Email
mmimeault@unmc.edu
Published
2007-00-00
Pages
981-1011
Language
English
Region
England
NLM ID
101083777
PMCID
PMC4401269
Subset
IM
Grants
NCI NIH HHS · U01 CA111294 · United States
NCI NIH HHS · CA72712 · United States
NCI NIH HHS · R01 CA078590 · United States
NCI NIH HHS · CA78590 · United States
NCI NIH HHS · P50 CA072712 · United States
NCI NIH HHS · CA111294 · United States
External Links
PubMed source DOI: 10.1111/j.1582-4934.2007.00088.x PMC Full Text View journal details
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