Abstract
G-quadruplexes are non-canonical secondary structures formed within nucleic acids that are involved in modulating cellular processes such as replication, gene regulation, recombination and epigenetics. Within genes, there is mounting evidence of G-quadruplex involvement in transcriptional and post transcriptional regulation. We report the presence of potential G-quadruplex motifs within relevant sites of some important pharmacogenes and discuss the possible implications of this on the function and expression of these genes. Appreciating the location and potential functions of these motifs may be of value when considering the impacts of some pharmacogenetic variants. G-quadruplexes are also the focus of drug development efforts in oncology and we highlight the broader pharmacological implications of treatment strategies that may target G-quadruplexes.
Highlights
The desire to implement pharmacogenetic testing as a means to improve drug safety and treatment efficacy has led to intense scrutiny of the functional and clinical relevance of variation in pertinent genes (Sim et al, 2013)
Small molecule based G4 binding ligands have proved successful in regulating transcription and expression of proto-oncogenes, providing a novel approach to the treatment of cancerous cells (Siddiqui-Jain et al, 2002; Gunaratnam et al, 2009)
While G4s located in regulatory regions of pharmacogenes may provide opportunities for pharmacokinetic modulation by small molecules that target G4, they represent a risk for off-target regulatory effects of chemotherapeutics designed to target regulatory G4 in oncogenes
Summary
The desire to implement pharmacogenetic testing as a means to improve drug safety and treatment efficacy has led to intense scrutiny of the functional and clinical relevance of variation in pertinent genes (Sim et al, 2013). Addition of small molecule ligands was found to stabilize G4s in the promoters of the proto-oncogene RET (Shin et al, 2014) and the gene encoding tumor angiogenesis factor VEGF (Salvati et al, 2014) resulting in altered protein expression.
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