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2017 ; 8
(5
): 8854-8866
Nephropedia Template TP
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English Wikipedia
Improving anticancer drug development begins with cell culture: misinformation
perpetrated by the misuse of cytotoxicity assays
#MMPMID27750219
Eastman A
Oncotarget
2017[Jan]; 8
(5
): 8854-8866
PMID27750219
show ga
The high failure rate of anticancer drug discovery and development has consumed
billions of dollars annually. While many explanations have been provided, I
believe that misinformation arising from inappropriate cell-based screens has
been completely over-looked. Most cell culture experiments are irrelevant to how
drugs are subsequently administered to patients. Usually, drug development
focuses on growth inhibition rather than cell killing. Drugs are selected based
on continuous incubation of cells, then frequently administered to the patient as
a bolus. Target identification and validation is often performed by gene
suppression that inevitably mimics continuous target inhibition. Drug
concentrations in vitro frequently far exceed in vivo concentrations. Studies of
drug synergy are performed at sub-optimal concentrations. And the focus on a
limited number of cell lines can misrepresent the potential efficacy in a patient
population. The intent of this review is to encourage more appropriate
experimental design and data interpretation, and to improve drug development in
the area of cell-based assays. Application of these principles should greatly
enhance the successful translation of novel drugs to the patient.
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