DNA Methylation Biomarkers for Prediction of Response to Platinum-Based Chemotherapy: Where Do We Stand?

SIMPLE SUMMARY: Platinum-based agents are one of the most widely used chemotherapy drugs for various types of cancer. However, one of the main challenges in the application of platinum drugs is resistance, which is currently being widely investigated. Epigenetic DNA methylation-based biomarkers are promising to aid in the selection of patients, helping to foresee their platinum therapy response in advance. These biomarkers enable minimally invasive patient sample collection, short analysis, and good sensitivity. Hence, improved methodologies for the detection and quantification of DNA methylation biomarkers will facilitate their use in the choice of an optimal treatment strategy. ABSTRACT: Platinum-based chemotherapy is routinely used for the treatment of several cancers. Despite all the advances made in cancer research regarding this therapy and its mechanisms of action, tumor resistance remains a major concern, limiting its effectiveness. DNA methylation-based biomarkers may assist in the selection of patients that may benefit (or not) from this type of treatment and provide new targets to circumvent platinum chemoresistance, namely, through demethylating agents. We performed a systematic search of studies on biomarkers that might be predictive of platinum-based chemotherapy resistance, including in vitro and in vivo pre-clinical models and clinical studies using patient samples. DNA methylation biomarkers predictive of response to platinum remain mostly unexplored but seem promising in assisting clinicians in the generation of more personalized follow-up and treatment strategies. Improved methodologies for their detection and quantification, including non-invasively in liquid biopsies, are additional attractive features that can bring these biomarkers into clinical practice, fostering precision medicine.