Author(s) name and affiliation:
Hanh H. Le1, Joshua A. Bittker1, Jaime H. Cheah1, Edmund V. Price1, Michelle Palmer1, Alykhan F. Shamji1, Stuart L. Schreiber1,2
1Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142; 2Howard Hughes Medical Institute, Chemistry & Chemical Biology, Harvard University, Cambridge, MA 02142
Poster Abstract : Increasing the throughput of small-molecule cancer cell-line profiling
Small-molecule sensitivity profiling of large numbers of cancer cell lines, when correlated with genetic features, enables the generation of hypotheses about what targets and pathways may be promising for therapeutic intervention in cancers with a given genotype. However, the power of this analysis and the confidence of the conclusions are heavily dependent on the number of cell lines used. As part of the CTD2 network, the Broad Institute has tested a set of ~200-250 small-molecule probes in over 150 cell lines towards a goal of 1000 lines. Currently the time needed to characterize the sensitivity of this many lines exceeds a year, which limits both the inclusion of newly identified probes and the ability to generate complete datasets. We have therefore begun investigating the application of additional high-throughput screening (HTS) methods to cell-line profiling. These include automated tissue culture robotics, acoustic dispensing of pre-printed compounds in assay plates, and the use of bead-based 3-dimensional cell culture. The latter method may be particularly valuable in enabling the handling of cell lines as a common reagent, circumventing a major bottleneck in the current process. The ability to handle a variety of bead-based cell-lines as a screening reagent makes profiling more similar to traditional HTS and enables use of many well-developed screening techniques. We anticipate that application of these techniques would increase profiling throughput several fold, greatly reducing the time needed to profile >1000 cell lines and enabling improved generation and analysis of data.
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