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Portal Launched Matching Cancer Cells to Drug Molecules

Genomics illustration

(NIH.gov)

The Broad Institute, a medical research organization with scientists from Harvard University and Massachusetts Institute of Technology, opened its Cancer Therapeutics Response Portal, an online resource that matches potential drug molecules to their sensitivities among hundreds of cancer cell lines. The portal is described this week in the journal Cell (paid subscription required), in an article by Broad Institute’s Stuart Schreiber, with colleagues from Broad, Vanderbilt, and Columbia universities.

The portal provides quantitative measurements of sensitivity from 242 cancer cell lines, characterized by their genomic properties. Those sensitivity measurements are then connected to a set of 354 small molecules — called an informer set — that target cancer cell circuitry. Among those molecules are 35 drugs approved by FDA, with another 54 candidates.

The result, says Broad Institute, is more than 76,000 connections between genetic features of cancer cell lines and their sensitivity to specific small molecules. Each of small molecules in the database targets one or more specific nodes in cancer cell circuitry and thus affect the behavior of cancer cells. The database identifies statistically significant correlations between cancer cell properties and sensitivities to the small molecules.

Genomic characteristics of the portal’s cell lines are derived from a companion project, the Cancer Cell Line Encyclopedia, a collaboration between the pharmaceutical company Novartis and Broad Institute. The encyclopedia contains computational analyses of some 1,000 cancer cell lines , including mutations, gene expression, and other genomic alterations in each cancer cell line.

Those genomic alterations can be important in understanding the transformation of healthy cells to cancer cells, as they gain proteins that promote unchecked growth. The portal’s database is expected to identify drug molecules addressing those proteins that may not have been previously considered. At the same time, the database can disclose new protein targets for those molecules.

Schreiber calls the Cancer Therapeutics Response Portal “a hypothesis-generating resource that will accelerate the discovery of new small-molecule therapeutics targeting different subsets of cancer.” The project is supported by the Cancer Target Discovery and Development program of National Cancer Institute that aims to bridge the gap between the volumes of genomic data and their application to cancer therapies.

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