Clinical use of biomarkers in the field of cytotoxic nucleoside analogues

ObjectivesCytotoxic nucleosides (gemcitabine, cytarabine horizontal ellipsis ) are used for the treatment of various malignancies. Their activity is dependent on the interaction with several proteins and enzymes of nucleotide metabolism. It has for a long time been hypothesized that the clinical activity of nucleoside analogues can be predicted by studying corresponding genes or gene products in clinical samples.MethodsIn this short review, I will present old and new published data from our group and others about the prediction of activity of these drugs concentrating on gene-candidate approaches, and discuss biological and technical limitations of these.ResultsA large number of studies have been conducted in various clinical settings (drugs, disease, patient cohort horizontal ellipsis ) evaluating DNA, mRNA or protein-related markers. Although some individual parameters and associations thereof have been validated, only a very few numbers have been implemented in pretreatment evaluations of patients.ConclusionThere is still much to do in the field of outcome-prediction with nucleoside analogues. The use of multiparametric methods could increase the success rate but at the cost of a poorer understanding of molecular mechanisms.

Automated summary

There is still much to be done in the field of predicting the outcomes of nucleoside analogues. The use of multiparametric methods could improve the success rate, but at the cost of a poorer understanding of molecular mechanisms.