Journal of cellular and molecular medicine
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.
Animals, Disease Progression, Drug Resistance, Neoplasm, Humans, Neoplasms, Neoplastic Stem Cells
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Recent advances in cancer stem/progenitor cell research: Therapeutic implications for overcoming resistance to the most aggressive cancers/Mimeault, Hauke, Mehta & Batra/Journal of Cellular and Molecular Medicine 11(5). Copyright © 2007 The Authors Journal of Cellular and Molecular Medicine Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
Mimeault, M.; Hauke, Ralph; Mehta, Parmender P.; and Batra, Surinder K., "Recent advances in cancer stem/progenitor cell research: therapeutic implications for overcoming resistance to the most aggressive cancers." (2007). Journal Articles: Biochemistry & Molecular Biology. 94.