Types of targets identified through comprehensive genome and transcriptome analysis of cancer cells.

Most genetic targets will result from a "gain of expression," as in the case of genes that are activated by either a point mutation or a chromosomal rearrangement that creates a new protein sequence. Targets can also be proteins with a normal sequence that are pathologically overexpressed by genomic amplifications, promoter mutations, or upstream pathway activation. An example is the discovery of epidermal growth factor receptor (EGFR) genomic amplification, leading to its overexpression and increased kinase activity, which can be targeted by small molecules. Designing compounds that are toxic to cells on the basis of "loss of expression" might be an alternative way to target cancer cells; this approach could be adopted in the case of missing tumor-suppressor proteins, a genetic event that is common in tumor development.