RT Journal Article
SR Electronic
T1 Methods for High-Throughput Drug Combination Screening and Synergy Scoring
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 051698
DO 10.1101/051698
A1 Liye He
A1 Evgeny Kulesskiy
A1 Jani Saarela
A1 Laura Turunen
A1 Krister Wennerberg
A1 Tero Aittokallio
A1 Jing Tang
YR 2016
UL http://biorxiv.org/content/early/2016/05/05/051698.abstract
AB Gene products or pathways that are aberrantly activated in cancer but not in normal tissue hold great promises for being effective and safe anticancer therapeutic targets. Many targeted drugs have entered clinical trials but so far showed limited efficacy mostly due to variability in treatment responses and often rapidly emerging resistance. Towards more effective treatment options, we will critically need multi-targeted drugs or drug combinations, which selectively inhibit the cancer cells and block distinct escape mechanisms for the cells to become resistant. Functional profiling of drug combinations requires careful experimental design and robust data analysis approaches. At the Institute for Molecular Medicine Finland (FIMM), we have developed an experimental-computational pipeline for high-throughput screening of drug combination effects in cancer cells. The integration of automated screening techniques with advanced synergy scoring tools allows for efficient and reliable detection of synergistic drug interactions within a specific window of concentrations, hence accelerating the identification of potential drug combinations for further confirmatory studies.