At present, most drug screening efforts employ bulk cancer cell populations, which may lead to selection of the more drug-resistant cancer stem cells (CSCs). However, drug screening using CSCs has been limited, mainly owing to the difficulty of their isolation. This article discusses how methods of reprogramming cancer cells to primitive cancer cell states, such as transcription factor reprogramming, epithelial-mesenchymal transition (EMT), conditional reprogramming, and hypoxia, may approach the CSC state and thus be relevant for drug screening purposes. This leads to the importance of recapitulating the stem cell niche in drug assays, which is enabled by recent advances in cell culture and tissue engineering. With the advent of these technologies, this article addresses the question of whether the stem cell phenotype should be targeted for drug screening.
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