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

Journal of Cellular and Molecular Medicine - Tập 11 Số 5 - Trang 981-1011 - 2007
Murielle Mimeault1,2, Ralph J. Hauke3,2, Parmender P. Mehta1,2, Surinder K. Batra1,4,2
1Department of Biochemistry and Molecular Biology, Eppley Institute of Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA
2Eppley Institute of Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA
3Division of Hematology and Oncology, Department of Internal Medicine, Eppley Institute of Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA
4Department of Pathology and Microbiology, Eppley Institute of Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA

Tóm tắt

Introduction Functions of cancer progenitor cells in the cancer initiation and progression New model of carcinogenesis based on the cancer progenitor cells Isolation and ex vitro and in vivo characterization of functional properties of cancer progenitor cells Functions of cancer progenitor cells in the cancer development Influence of local tumour microenvironment on the behavior of cancer progenitor cells Cancer types originating from cancer progenitor cells New concepts of the heterogeneity of cancers derived from distinct cancer progenitor cells Implication of cancer progenitor cells in bone marrow‐derived cancers Leukaemias Sarcomas Implication of cancer progenitor cells in pediatric and adult brain tumors Implication of cancer progenitor cells in other cancer types Novel cancer therapies by molecular targeting of cancer progenitor cells and their microenvironment New concepts on the functions of cancer progenitor cells in the resistance to current cancer therapies New combination therapies against the aggressive and recurrent cancers Targeting cancer progenitor cells Targeting the local microenvironment of cancer progenitor cells Conclusions Future directions and perspectives AbstractOvercoming 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/β ‐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.

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Journal of Cellular and Molecular Medicine

Tập 11 Số 5

981-1011

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