DTP Branches and Offices
Small-molecule Investigational Oncology Agents
As part of its mission, the Drug Synthesis and Chemistry Branch acquires samples of investigational oncology agents, comprised primarily of targeted small molecules currently in clinical and/or preclinical anticancer studies, for evaluation in the NCI-60 cell-line screen. As oncology treatment moves toward personalized targeted therapeutic agents, the NCI-60 human tumor cell line panel is an ideal community-wide tool to further understanding of the disease targets of new agents. The panel includes cell lines from nine tumor types, and is extremely well characterized at the molecular level, with both in-house and crowd-sourced characterization, including exome sequence for mutations, SNPs, DNA methylation, metabolome, mRNA, microRNA, and protein expression. This molecular characterization dataset enables interrogation of patterns of growth inhibition by the investigational drug set looking for characteristics of the cell lines that determine sensitivity. It is anticipated that comparison between drug sensitivity profiles from this data set could lead to the elucidation of common mechanistic targets or pathways, associations with potential response biomarkers, the confirmation of mechanism of action or identification of novel mechanisms, and the uncovering of unexpected “off-target” activities.
DSCB is in the process of developing open-source web-based online tools to enable data analysis for this set, including an improved version of COMPARE (for current version, see: http://dtp.cancer.gov/databases_tools/compare.htm), which provides for the identification of compounds and/or genes that have highly correlated response patterns for any selected ‘seed’ compound.
Solid samples (5 mg) of most FDA-approved oncology drugs are available for transfer to external investigators for non-clinical research purposes (see procedure to obtain vialed samples). A plated set of the most current FDA-approved drugs is also available for transfer (see procedure to obtain plated sets).