Quaranta and his colleagues have developed a new metric to evaluate a compound's effect on cell proliferation, called the DIP (drug-induced proliferation) rate, that overcomes the flawed bias in the traditional method. For more than 30 years, scientists have evaluated the ability of a compound to kill cells by adding the compound to cells and counting how many cells are alive after 72 hours. But these "proliferation assays" that measure cell number at a single time point don't take into account the bias introduced by exponential cell proliferation, even in the presence of the drug. The findings have particular importance in light of recent international efforts to generate data sets that include the responses of "thousands of cell lines to hundreds of compounds," Quaranta said. The Cancer Cell Line Encyclopedia (CCLE) and Genomics of Drug Sensitivity in Cancer (GDSC) databases include drug response data along with genomic and proteomic data that detail each cell line's molecular makeup. The researchers evaluated the responses of four different melanoma cell lines to the drug Vemurafenib, currently used to treat melanoma, with the standard metric, used for the CCLE and GDSC databases, and with the DIP rate. In one cell line, they found a stark disagreement between the two metrics. A software package that will be available to other researchers through a hyperlink in the Nature Methods paper. Quaranta is working with the Vanderbilt Center for Technology Transfer and Commercialization to identify commercial entities that can further refine the software and make it widely available to the research community to inform drug discovery.
Friday, May 6, 2016
Researchers develop new approach to assess Cancer drug sensitivity in cells
"More than 90 percent of candidate Cancer drugs fail in late stage
clinical trials, costing hundreds of millions of dollars," said Vito
Quaranta, M.D., director of the Quantitative Systems Biology Center at
Vanderbilt. "The flawed in vitro drug discovery metric may not be the
only responsible factor, but it may be worth pursuing an estimate of its
impact."
Quaranta and his colleagues have developed a new metric to evaluate a compound's effect on cell proliferation, called the DIP (drug-induced proliferation) rate, that overcomes the flawed bias in the traditional method. For more than 30 years, scientists have evaluated the ability of a compound to kill cells by adding the compound to cells and counting how many cells are alive after 72 hours. But these "proliferation assays" that measure cell number at a single time point don't take into account the bias introduced by exponential cell proliferation, even in the presence of the drug. The findings have particular importance in light of recent international efforts to generate data sets that include the responses of "thousands of cell lines to hundreds of compounds," Quaranta said. The Cancer Cell Line Encyclopedia (CCLE) and Genomics of Drug Sensitivity in Cancer (GDSC) databases include drug response data along with genomic and proteomic data that detail each cell line's molecular makeup. The researchers evaluated the responses of four different melanoma cell lines to the drug Vemurafenib, currently used to treat melanoma, with the standard metric, used for the CCLE and GDSC databases, and with the DIP rate. In one cell line, they found a stark disagreement between the two metrics. A software package that will be available to other researchers through a hyperlink in the Nature Methods paper. Quaranta is working with the Vanderbilt Center for Technology Transfer and Commercialization to identify commercial entities that can further refine the software and make it widely available to the research community to inform drug discovery.
Quaranta and his colleagues have developed a new metric to evaluate a compound's effect on cell proliferation, called the DIP (drug-induced proliferation) rate, that overcomes the flawed bias in the traditional method. For more than 30 years, scientists have evaluated the ability of a compound to kill cells by adding the compound to cells and counting how many cells are alive after 72 hours. But these "proliferation assays" that measure cell number at a single time point don't take into account the bias introduced by exponential cell proliferation, even in the presence of the drug. The findings have particular importance in light of recent international efforts to generate data sets that include the responses of "thousands of cell lines to hundreds of compounds," Quaranta said. The Cancer Cell Line Encyclopedia (CCLE) and Genomics of Drug Sensitivity in Cancer (GDSC) databases include drug response data along with genomic and proteomic data that detail each cell line's molecular makeup. The researchers evaluated the responses of four different melanoma cell lines to the drug Vemurafenib, currently used to treat melanoma, with the standard metric, used for the CCLE and GDSC databases, and with the DIP rate. In one cell line, they found a stark disagreement between the two metrics. A software package that will be available to other researchers through a hyperlink in the Nature Methods paper. Quaranta is working with the Vanderbilt Center for Technology Transfer and Commercialization to identify commercial entities that can further refine the software and make it widely available to the research community to inform drug discovery.
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