An analysis by NTRC of 122 anti-cancer agents is cover story of Molecular Cancer Therapeutics, a leading journal on cancer drug discovery from the American Association of Cancer Research (AACR). The article on comparative profiling is marked by the editors as one of the highlights of the December issue, which appeared in print last Friday.

In the article NTRC scientists describe the comparative analysis of the anti-proliferative activity of 122 publicly known anti-cancer agents in the Oncolines™ cell panel. The compounds studied include many recently approved targeted therapies, cytotoxic agents, and epigenetic modulators. For 38 compounds this is the first cancer cell panel profiling study. Good correlations were observed with other cell panels. This is illustrated with the cover image, which shows a Pearson correlation matrix of 51 anti-cancer agents that have been analysed in Oncolines™ panel and in the cell panel from the National Cancer Institute (NCI-60).

In the article on page 3097 Uitdehaag and colleagues show that the 122 anti-cancer agents can be arranged in twenty-six clusters of compounds with common mechanisms of action. This ‘hierarchical clustering’ includes nine clusters that have not been reported before, such as clusters of inhibitors of EZH2, bromodomain (BET) and the spindle assembly checkpoint kinase TTK (Mps1). The lack of clustering of several Aurora and PI3K inhibitors could be explained by differences in biochemical selectivity. Different clustering of PI3K and mTOR inhibitors corresponded with different genomic targeting. The study shows that cell line profiling is an excellent tool for the unbiased classification of anti-proliferative compounds.

Comparative cell panel profiling (OncolinesProfiler™) is part of the Oncolines™ cancer cell line profiling service of NTRC. Comparative profiling can provide more insight into the mechanism of action of new candidate drugs, and can be used to determine similarity or differentiation of new compounds from existing anti-cancer agents.

Reference: Uitdehaag et al. (2016) Cell panel profiling reveals conserved therapeutic clusters and differentiates the mechanism of action of different PI3K/mTOR, Aurora kinase and EZH2 inhibitors. Molecular Cancer Therapeutics 15 (12), 3097-3109.