| Figu
res/TablesFigu
res/Tables | Refe
rencesRefe
rencesrsion="1.0" encoding="UTF-8"?>
Summary
Selective ta
rgeting of cance
r stem cells (CSCs) offe
rs p
romise fo
r a new gene
ration of the
rapeutics. Howeve
r, assays fo
r both human CSCs and no
rmal stem cells that a
re amenable to
robust biological sc
reens a
re limited. Using a discove
ry platfo
rm that
reveals diffe
rences between neoplastic and no
rmal human plu
ripotent stem cells (hPSC), we identify small molecules f
rom lib
ra
ries of known compounds that induce diffe
rentiation to ove
rcome neoplastic self-
renewal. Su
rp
risingly, thio
ridazine, an antipsychotic d
rug, selectively ta
rgets the neoplastic cells, and impai
rs human somatic CSCs capable of in聽vivo leukemic disease initiation while having no effect on no
rmal blood SCs. The d
rug antagonizes dopamine
recepto
rs that a
re exp
ressed on CSCs and on b
reast cance
r cells as well. These
results suggest that dopamine
recepto
rs may se
rve as a bioma
rke
r fo
r dive
rse malignancies, demonst
rate the utility of using neoplastic hPSCs fo
r identifying CSC-ta
rgeting d
rugs, and p
rovide suppo
rt fo
r the use of diffe
rentiation as a the
rapeutic st
rategy.
PaperClip
ryStr="" href="#mmc4">