选择性靶向肿瘤干细胞（CSCs）为新一代治疗带来了希望。然而，研究者一直缺乏针对人类肿瘤干细胞和正常干细胞高效的生物学筛选手段。5月23日Cell杂志在线发表了Eleftherios Sachlos等的研究论文，为CSCs研究者提供了新的研究手段。
应用一项揭示人类癌性和正常多能干细胞之间差异的研究平台，他们从已知化合物文库中确定了一些可诱导分化，并抑制癌性自我更新的小分子化合物。令人惊讶的是，一种叫甲硫哒嗪的抗精神病药物，可在不伤害正常造血干细胞的情况下，抑制白血病干细胞在体内的成癌作用。这种药物抑制表达于CSCs和乳腺癌细胞表面的多巴胺受体。
这项研究提示，多巴胺受体也许可以作为多种癌症的生物标志物。同时证实，运用癌性人类多能干细胞来筛选CSC靶向性药物，是一条行之有效的研究手段。可为分化治疗提供有力的研究支持。(生物谷Bioon.com)
doi:10.1016/j.cell.2011.10.017
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Identification of Drugs Including a Dopamine Receptor Antagonist that Selectively Target Cancer Stem Cells
Bhatia and colleagues
Selective targeting of cancer stem cells (CSCs) offers promise for a new generation of therapeutics. However, assays for both human CSCs and normal stem cells that are amenable to robust biological screens are limited. Using a discovery platform that reveals differences between neoplastic and normal human pluripotent stem cells (hPSC), we identify small molecules from libraries of known compounds that induce differentiation to overcome neoplastic self-renewal. Surprisingly, thioridazine, an antipsychotic drug, selectively targets the neoplastic cells, and impairs human somatic CSCs capable of in vivo leukemic disease initiation while having no effect on normal blood SCs. The drug antagonizes dopamine receptors that are expressed on CSCs and on breast cancer cells as well. These results suggest that dopamine receptors may serve as a biomarker for diverse malignancies, demonstrate the utility of using neoplastic hPSCs for identifying CSC-targeting drugs, and provide support for the use of differentiation as a therapeutic strategy.
