Multidimensional profiling in the investigation of small-molecule-induced cell death

Numerous morphological variations of cell death have been described. These processes depend on a complex and overlapping cellular signaling network, making molecular definition of the pathways challenging. This review describes one solution to this problem for small-molecule-induced death, the creation of high-dimensionality profiles for compounds that can be used to define and compare pathways. Such profiles have been assembled from gene expression measurements, protein quantification, chemical-genetic interactions, chemical combination interactions, cancer cell line sensitivity profiling, quantitative imaging, and modulatory profiling. We discuss the advantages and limitations of these techniques in the study of cell death.