Prognostic Value of Circulating Tumor DNA (ctDNA) in Oncogene-Driven NSCLC: Current Knowledge and Future Perspectives

SIMPLE SUMMARY: Personalized medicine has significantly changed the clinical outcome of oncogene-driven non-small cell lung cancer (NSCLC) due to the efficacy of molecular targeted therapies. Despite the advances in the management of this group of patients, the need for powerful biomarkers with the potential for a real-time assessment of the tumor genomic profile as well as for detecting and monitoring minimal residual disease (MRD) remains unmet. The aim of this article is to present the current knowledge and the future perspectives regarding the prognostic value of ctDNA in NSCLC, focusing on the most common druggable driver mutations, including those in epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1), rearranged during transfection (RET), kirsten rat sarcoma virus (KRAS), B-Raf proto-oncogene (BRAF), and mesenchymal epithelial transition factor receptor (MET) genes. ABSTRACT: As we enter an unprecedented era of personalized medicine, molecular targeted therapies have the potential to induce improved survival outcome in patients with non-small cell lung cancer (NSCLC). However, a significant percentage of oncogene-driven NSCLC patients will relapse even after definitive treatment, whereas chronic and durable response to targeted therapies is a less common event in advanced-stage lung cancer. This phenomenon could be attributed to minimal residual disease (MRD), defined as a population of disseminated tumor cells that survive during the course or after treatment, eventually leading to recurrence and limiting patient survival. Circulating tumor DNA (ctDNA) is a powerful biomarker for MRD detection and monitoring and is a non-invasive approach of treating cancer, and especially NSCLC, based on a real-time assessment of the tumor genomic landscape. In this review, we present the key findings of studies that have used ctDNA with regard to its prognostic value and in respect to the most common druggable driver mutations of genes in NSCLC, such as epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1), rearranged during transfection (RET), Kirsten rat sarcoma virus (KRAS), B-Raf proto-oncogene (BRAF), and mesenchymal epithelial transition factor receptor (MET).