Developed by the Broad Institute of MIT and Harvard, PRISM (Profiling Relative Inhibition Simultaneously in Mixtures) is a novel DNA barcoding technology that allows for rapid, viability screening of more than 900 human cancer cell-line models in mixtures. These 900 cell lines represent more than 45 major lineages of cancer.
Traditional cell line viability screening is done one cell line at a time, requiring lots of time and reagents, which can slow down drug discovery and development efforts. PRISM’s unique approach to barcoding and pooling cell lines for high-throughput screening overcomes the limitations of single cell line studies, helping researchers rapidly collect cancer cell line drug-sensitivity data on an unprecedented scale.
The true power of PRISM is not only viability screening of a large number of cell lines, it is their genomic characterization. Through the Cancer Cell Line Encyclopedia efforts and now the Dependency Map efforts we have genomically profiled and identified genetic dependencies for the PRISM cell set. We compare the viability profile of your drug with these baseline genomic features and genetic dependencies to identify the patient population and target of your drug. PRISM screening can be used to:
- Confirm the mechanism of action of your drug
- Uncover novel drug mechanisms of action
- Identify unexpected off-target effects and toxicities
- Establish which patient populations might benefit from treatments
Our original efforts have been published by Channing Yu in 2016, to prove that mixing barcoded cell lines together is feasible and by Steven Corsello in 2020 showing that screening a large number of known drugs across over 500 barcoded cell lines identified new indications for non-oncology drugs.
PRISM has been collaborating with researchers in academia and industry since 2015. Through two large pharmaceutical collaborations we have screened over 30,000 compounds in 500 cell lines and dozens of compounds with academic researchers.
Our current cell set is over 900 cancer cell lines, that is available for anyone to screen three times per year. We now offer single agent small molecule, combination and aqueous screening. We have collaborated with over 150 academic and industrial collaborators in the last couple of years, many of them have screened multiple compounds with us.
First publication of the PRISM method from 2016. 102 cell lines were labeled with unique 24-nucleotide barcodes and used to screen 8400 compounds.
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An updated panel of 578 barcoded cancer cell lines were used to profile the activity of 4518 existing drugs. Results were used to begin the PRISM drug repurposing resource.
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