canSAR: an updated cancer research and drug discovery knowledgebase

Abstract

canSAR (http://cansar.icr.ac.uk) is a publicly available, multidisciplinary, cancer-focused knowledgebase developed to support cancer translational research and drug discovery. canSAR integrates genomic, protein, pharmacological, drug and chemical data with structural biology, protein networks and druggability data. canSAR is widely used to rapidly access information and help interpret experimental data in a translational and drug discovery context. Here we describe major enhancements to canSAR including new data, improved search and browsing capabilities, new disease and cancer cell line summaries and new and enhanced batch analysis tools.

Figure 1.

Molecular target synopsis: new features. (A) Curated chemical probes targeting BRD4. (B) BRD4 normalised expression (z-scores) across TCGA studies. Interactive comparison between normal (green bars) and primary tumour (blue bars) samples. Metastatic samples have been deselected in this example. (C) NCI60 and Gene Expression Atlas cell lines ranked by BRD4 expression. (D) Mutation incidence for BRD4 across COSMIC cell lines. Clicking on a cell line graph bar presents a detailed mutational profile for the gene. For example: (E) BRD4 mutations in colorectal cell lines.

Figure 2.

Disease synopsis: clinical trials. (A) Global summary of clinical trials with information on approved drugs, clinical candidates, chemical probes and cell lines models applicable to each particular cancer type. Clicking on the desired disease link, e.g. Prostate Cancer, reveals detailed information specific to the disease (B). This includes: (i) drugs and clinical candidates with chemical structure links to the detailed canSAR Compound Synopsis. (ii) Timelines for applicable clinical trials, that can be filtered, sorted and grouped by phase by the user. Hovering over a specific timeline displays a brief synopsis for the trial and the bar colour reflects the trial phase. (iii) Cell line models relevant to the disease with sortable links to the canSAR cell line synopsis pages.

Figure 3.

Cell line synopsis: similar cell lines. Apart from accessing the genetic, expression and pharmacological profile for a cell line of interest (e.g. PC-3), the user can also investigate which cell lines exhibit similar features such as (A) similarity across the cell line mutational spectrum and (B) overall or chromosome-specific copy number variation. In addition similarity can be assessed by gene expression or by drug sensitivity (not shown).

Figure 4.

Enhanced druggable protein networks. (A) Each interactor icon indicates the pharmacological potential and genetic information available in canSAR. (B) Dynamically generated interactome for EGFR, using phosphorylation reactions derived from Phosphosite (purple directed interactions) and transcriptional regulation (light blue directed interactions). Additional interaction types include Reactome Functional Interactions and molecular complexes. The network complexity can be controlled by the number of visible nodes. The network can be saved as an image or a json object for further analysis (e.g. in Cytoscape).