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Abundant evidence suggests that Wnt signaling is active in both
stem cell self-renewal and malignant proliferation of immature
tumor cells. This notion is particularly interesting in light
of recent evidence supporting the existence of cancer stem
cells. So-called cancer stem cells are distinct populations
of cells found within tumors and possess features typical of adult
stem cells such as self-renewal and capacity for
differentiation. Cell surface markers specific to lung cancer
stem cells have been identified in murine models, and our group is
looking to discover lung cancer stem cells in human tumors.
After performing both in vitro and in vivo (mouse model) cell
culture from surgically resected human lung tumors, we are using
cell sorting methods to identify human lung cancer stem
cells.
Future drug development will seek to identify compounds that are
toxic to these cancer stem cells. We recently proposed to
screen for small molecule inhibitors of Wnt-2 transcription through
our proprietary Wnt-2 reporter assay. The results of this
screen, we believe, will lead to therapies not only against
terminally differentiated cancer cells-the traditional target of
such agents-but also cancer stem cell populations, both driven by
aberrant Wnt activation. In conjunction with several of our
international collaborators, our lab has published a number of
important review papers on the topic of cancer stem cells, and we
are currently contributing to a book on the subject as well.