Circulating tumour DNA: A new biomarker to monitor resistance in NSCLC patients treated with EGFR-TKIs

Targeted molecular therapies have markedly improved the therapeutic management of lung cancer, while the discovery of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has revolutionized the treatment of non-small cell lung cancer (NSCLC). However, the clinical benefit of targeted therapies is limited by the eventual emergence of resistance. Identifying and monitoring the underlying mechanism of EGFR-TKI resistance could lead to more precise therapy and advances in treatment. Presently, tissue biopsy remains the gold standard for genotyping but it is limited by sampling bias, lack of available tissue, and potential complications. Analysis of circulating tumour DNA (ctDNA) may overcome the current limitations of tissue biopsies and provide a comprehensive landscape of the resistance mechanisms in a minimally invasive manner. Well-developed, analytically valid detection technologies are prerequisites for integrating ctDNA detection into clinical cancer management. Here, we provide an overview of available methodologies for ctDNA detection and we also discuss the potential clinical applications of ctDNA to monitor the resistance mechanisms.