Genomics of drug sensitivity in bladder cancer: an integrated resource for pharmacogenomic analysis in bladder cancer

Abstract

Background: Bladder cancer has numerous genomic features that are potentially actionable by targeted agents. Nevertheless, both pre-clinical and clinical research using molecular targeted agents have been very limited in bladder cancer.

Results: We created the Genomics of Drug Sensitivity in Bladder Cancer (GDBC) database, an integrated database (DB) to facilitate the genomic understanding of bladder cancer in relation to drug sensitivity, in order to promote potential therapeutic applications of targeted agents in bladder cancer treatment. The GDBC database contains two separate datasets: 1) in-house drug sensitivity data, in which 13 targeted agents were tested against 10 bladder cancer cell lines; 2) data extracted and integrated from public databases, including the Cancer Therapeutics Research Portal, Cancer Cell Line Encyclopedia, Genomics of Drug Sensitivity in Cancer, Kyoto Encyclopedia of Genes and Genomes, and the Cancer Gene Census databases, as well as bladder cancer genomics data and synthetic lethality/synthetic dosage lethality connections.

Conclusions: GDBC is an integrated DB of genomics and drug sensitivity data with a specific focus on bladder cancer. With a user-friendly web-interface, GDBC helps users generate genomics-based hypotheses that can be tested experimentally using drugs and cell lines included in GDBC.

Keywords: Bladder cancer; Database; Drug response; Pharmacogenomics; Therapeutic biomarker.

Fig. 1

The schematic representation of GDBC. GDBC consists of two parts: 1) in-house drug sensitivity data; 2) data extracted from public databases. a The genomic features of bladder cancer were extracted from CCLE and the literature. b The drug sensitivity data were partly extracted from CTRP, GDSC and CCLE and were partly generated in-house using 13 targeted agents against 10 bladder cancer cell lines. c SL and SDL connections were calculated using the genomic features of bladder cancer cell lines (refer to the Methods section). d Pathway and cancer gene data were extracted from the KEGG and Cancer Gene Census, respectively. A web interface was developed for user-friendly access to GDBC

Fig. 2

Drug sensitivity of EGFR inhibitors in bladder cancer cell lines. Bladder cancer cell lines with high expression of EGFR, including HT1376, 5637 and UBLC1, were markedly sensitive to EGFR-targeting agents. The average IC50 is the average sensitivity of those drugs in different available cell lines across CTRP