Research ArticleDRUG TESTING

Multi-organ system for the evaluation of efficacy and off-target toxicity of anticancer therapeutics

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Science Translational Medicine  19 Jun 2019:
Vol. 11, Issue 497, eaav1386
DOI: 10.1126/scitranslmed.aav1386

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Testing for toxicity

Standard methods of in vitro preclinical drug testing can be useful to detect cytotoxicity and evaluate safety pharmacology but fail to capture effects of drug metabolites (including functional effects) that become apparent at the organ systems level. McAleer et al. constructed an in vitro system using multiple human cancer and healthy cell types from different organs and recirculating serum-free medium. Within the system, anticancer drugs including tamoxifen, diclofenac, imatinib, and verapamil demonstrated variable on-target and off-target effects, some of which were dependent on drug metabolism by liver cells. This study supports the use of simple yet versatile multi-organ cell-based systems for efficient preclinical drug testing.

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