Targeting hedgehog in cancer stem cells: how a paradigm shift can improve treatment response.
The integration of developmental biology and cancer therapeutics has revolutionized the understanding of tumor proliferation. Cell-signaling pathways first recognized for their importance in embryogenesis have begun to inspire the scientific community to investigate new avenues in cancer initiation and growth. Other ground-breaking discoveries provided evidence for a revisit to the theory of cancer stem cells, which has long-term implications for the efficient and lasting elimination of cancer. This paradigm shift involves a change from viewing the malignant tumor as a perpetually mutating mass of clonogenic cells to seeing it as an organ mistakenly created by mutations that disrupt cell-signaling pathways in stem cells. As researchers find more evidence of the essential involvement of these signaling pathways in cancer formation and maintenance, the link between tumorigenesis and aberrant stem cell activation can be more clearly drawn. One such pathway is the hedgehog (Hh)-signaling pathway, which is important in growth and differentiation during embryogenesis and for proper functioning in many adult tissues. Investigation of this pathway and its involvement in cancer has already led to drug development that could eradicate basal cell carcinoma, the most common type of cancer in humans. Future research focused on Hh and related signaling pathways involved in cancer might improve treatment response in malignancies resistant to traditional therapy.
Tung
David C Y
DC
The University of Texas, Department of Radiation Oncology, MD Anderson Cancer Center, Houston, TX 77030, USA.
Chao
K S Clifford
KS
D000818:Animals; D018432:Drug Resistance, Multiple; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction
D053823:Hedgehog Proteins