Complexities of pharmacogenomic interactions in cancer

Abstract

Genetic and genomic alterations drive cancer development. However, they may also constitute vulnerabilities, including increased drug sensitivity, which could be harnessed for precision medicine purposes. We discuss the highly complex pharmacogenomic interactions that are beginning to be disentangled and hurdles that may need to be overcome before cancer patients could benefit.

Keywords: Cancer; drug resistance; drug response; drug sensitivity; genomic instability; pharmacogenomics; precision medicine.

Figure 1.

Complex pharmacogenomic interactions in cancer cells. Meta-analysis of recently identified pharmacogenomic interactions in cancer cell lines,⁸ including mutations (mut), focal copy number alterations (fCNAs) and chromosome arm aneuploidies (CAAs) – the latter two including gains and losses. Pie charts show the distributions of interactions involving single genomic events (a) and pairs of co-occurring genomic events (b). Ratios of events involving gain and loss (G:L) are shown above each pie chart. Heatmaps show the frequencies of co-occurring events involved in drug interactions. Events associated with increased drug sensitivity or resistance are shown against green and red backgrounds, respectively. Source data are in Suppl. Data 10 and 11 of reference ⁸.