Genomics of Drug Sensitivity in Cancer

Summary Information

Targeted molecular therapies that disrupt specific intracellular signaling pathways are increasingly used for the treatment of cancer. The rational for this approach is based on our increasing understanding of the genes that are causally implicated in cancer and the clinical observation that the genetic features of a cancer can be predictive of patient response to targeted therapies. The goal of our project is to discover new cancer biomarkers that define subsets of drug-sensitive patients. Towards this aim we are screening a range of anti-cancer therapeutics against a large number of genetically characterized human cancer cell lines and correlating drug sensitivity with extensive genetic data. This information can be used to inform the optimal clinical application of cancer drugs as well as the design of clinical trials of investigational compounds being developed for the clinic.

The Genomics of Drug Sensitivity in Cancer Project is part of a unique 5-year collaboration between The Cancer Genome Project at the Wellcome Trust Sanger Institute (UK) and the Center for Molecular Therapeutics, Massachusetts General Hospital Cancer Center (USA). The Center for Molecular Therapeutics has pioneered the use of high-throughput platforms for examining the relationship between tumour cell genomics and sensitivity to anti-cancer agents. The Cancer Genome Project has led the way in the systematic analysis of cancer genomes to identify genes critical in the development of human cancers. This collaboration will develop and integrate the expertise at both sites toward the goal of identifying cancer biomarkers that can be used to identify genetically defined subsets of patients most likely to respond to targeted therapies.

As part of this collaboration, we plan to screen >1000 genetically characterised human cancer cell lines with a wide range of anti-cancer therapeutics. These compounds include classical chemotherapeutics as well as targeted therapeutics from commercial sources, academic collaborators, and from the biotech and pharmaceutical industries. The sensitivity patterns of the cell lines will be correlated with extensive genomic data to identify genetic features that are predictive of sensitivity. This large collection of cell lines enables us to capture much of the genomic heterogeneity that underlies human cancer, and which appears to play a critical role in determining the variable response of patients to treatment with specific agents. Our sensitivity data and genetic correlations are freely available through the COSMIC website as a resource to the academic and medical communities.