選擇性靶向腫瘤干細(xì)胞（CSCs）為新一代治療帶來了希望。然而，研究者一直缺乏針對人類腫瘤干細(xì)胞和正常干細(xì)胞高效的生物學(xué)篩選手段,。5月23日Cell雜志在線發(fā)表了Eleftherios Sachlos等的研究論文，為CSCs研究者提供了新的研究手段,。
應(yīng)用一項揭示人類癌性和正常多能干細(xì)胞之間差異的研究平臺，他們從已知化合物文庫中確定了一些可誘導(dǎo)分化,，并抑制癌性自我更新的小分子化合物。令人驚訝的是,，一種叫甲硫噠嗪的抗精神病藥物,，可在不傷害正常造血干細(xì)胞的情況下，抑制白血病干細(xì)胞在體內(nèi)的成癌作用,。這種藥物抑制表達(dá)于CSCs和乳腺癌細(xì)胞表面的多巴胺受體,。
這項研究提示，多巴胺受體也許可以作為多種癌癥的生物標(biāo)志物,。同時證實,，運用癌性人類多能干細(xì)胞來篩選CSC靶向性藥物，是一條行之有效的研究手段,?？蔀榉只委熖峁┯辛Φ难芯恐С帧?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.
