Despite groundbreaking advances in cancer research that have contributed to the development of effective cancer treatments, acquired resistance against initially effective treatments remains a persistent challenge. Resistance can arise through a variety of mechanisms, including gene mutation, gene overactivation and transporter-mediated drug efflux. For example, members of the ATP-binding cassette (ABC) transporter family have the ability to export different substrates, including drugs, across the cell membrane, which lowers their intracellular concentration and causes drug resistance.¹

To identify genes that may be involved in resistance to a drug of interest, Oncolines® cancer cell panel profiling in combination with GeneNominator™ gene expression analysis can be employed. Oncolines® cancer cell panel profiling is the parallel testing of compounds on a large panel of human cancer cell lines, which allows determination of half-maximal inhibitory concentration (IC₅₀) values through cell viability assays. In a GeneNominator™ gene expression analysis, the IC₅₀ values are correlated with the basal mRNA levels of many genes.

In a new case study on our website, we show the GeneNominator™ analysis results for a number of PARP inhibitors, whose cellular potencies were correlated with the gene expression levels of a subset of 420 genes known to be involved in drug resistance (e.g., ABC transporter genes). This study reveals distinctive correlations with ABC transporter genes for the different inhibitor types, and thereby demonstrates that Oncolines® cancer cell panel profiling in combination with the GeneNominator™ analysis can be used to identify drug transporters involved in resistance against novel therapeutics.