4:47 PM
Apr 16, 2018
 |  BC Extra  |  Tools & Techniques

Broad launches tool to identify vulnerabilities of cancer cells

The Broad Institute of MIT and Harvard University launched a publicly available online portal that allows any researcher worldwide to access and analyze data on genetic and pharmacologic dependencies of cancer cell lines, and associated molecular features. Compiled by Broad's Cancer Dependency Map, or DepMap, team, the portal could help identify new therapeutic targets aimed at specific vulnerabilities of cancer cells and the biomarkers that predict them. The portal was presented at the American Association for Cancer Research meeting in Chicago.

Broad said the portal's data exploration tool offers users, especially those with no computational background, an "easy and convenient way" to visualize data, such as discerning the relationship between dependency and expression of a gene of interest. It also provides "gene essentiality profiles for nearly every gene in the genome," as well as dependency profiles at genome scale across more than 500 human cell lines.

DepMap pools data from Broad’s Project Achilles; the Broad-Novartis Cancer Cell Line Encyclopedia; the Wellcome Trust Sanger Institute's Genomics of Drug Sensitivity and Cancer Project; and Project DRIVE from the Novartis Institute for BioMedical Research of Novartis AG (NYSE:NVS; SIX:NOVN).

A major theme at this year’s AACR is the abundance of preclinical discovery driven by molecular signatures identified in patient samples amassed by projects like Project Achilles (see BioCentury Innovations, April 12).

At AACR, Tango Therapeutics Inc. (Cambridge, Mass.) presented data showing a synthetic lethal interaction between AT rich interactive domain 1A (ARID1A), a component of the SWI/SNF chromatin remodeling complex that is frequently mutated in ovarian cancer, and hypoxia-inducible factor prolyl hydroxylase 2 (EGLN1; HIF-PH2; PHD2), an oxygen sensor that regulates hypoxia-inducible factor 1 alpha (HIF1A; HIF1-alpha). The company hypothesized the synthetic lethal relationship based on data from Project Achilles, which systematically characterizes gene essentiality via RNAi and CRISPR-Cas9 screens across hundreds of cancer cell lines

Also at the meeting, Pfizer Inc. (NYSE:PFE) launched the Variant Interpretation Portal (VIP), which systematically searches for associations that reveal synthetic lethal relationships in databases like Project Achilles and the Cancer Cell Line Encyclopedia, which is a compilation of gene expression, chromosomal copy number and sequencing data from 947 human cancer cell lines.

Project DRIVE outlines the results of nearly 8,000 gene knockdowns in roughly 400 patient derived cancer cell lines. The Genomics of Drug Sensitivity and Cancer Project captures the sensitivities and responses of more than 1,000 genetically characterized human cancer cell lines to anti-cancer therapeutics (see BioCentury Innovations, April 26, 2012 & BioCentury Extra, July 28, 2017).

Broad said tools for biomarker prediction and drug sensitivity data sets from the Broad Institute Cancer Target Discovery and Development Center will be added to the portal "shortly." The DepMap team will also release cell line genomic information and genome-wide CRISPR-Cas9 loss-of-function screen data on a quarterly basis.

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