How liquid biopsies can change clinical practice in oncology

Abstract

Cell-free DNA fragments are shed into the bloodstream by tumor cells. The analysis of circulating tumor DNA (ctDNA), commonly known as liquid biopsy, can be exploited for a variety of clinical applications. ctDNA is being used to genotype solid cancers non-invasively, to track tumor dynamics and to detect the emergence of drug resistance. In a few settings, liquid biopsies have already entered clinical practice. For example, ctDNA is used to guide treatment in a subset of lung cancers. In this review, we discuss how recent improvements in the sensitivity and accuracy of ctDNA analyses have led to unprecedented advances in this research field. We further consider what is required for the routine deployment of liquid biopsies in the clinical diagnostic space. We pinpoint technical hurdles that liquid biopsies have yet to overcome, including preanalytical and analytical challenges. We foresee how liquid biopsies will transform clinical practice: by complementing (or replacing) imaging to monitor treatment response and by detecting minimal residual disease after surgery with curative intent.

White blood cell and cell-free DNA analyses for detection of residual disease in gastric cancer

“…However, microscopic residual tumor, lymph node infiltration, and poor histopathological response do not measure the real-time presence of residual disease. More recent approaches such as detection of circulating tumor-derived DNA (ctDNA) through liquid biopsies may provide new opportunities for identifying patients that would benefit from adjuvant treatment options and further follow-up [9][10][11][12] .…”

Sequential analysis of transcript expression patterns improves survival prediction in multiple cancers

“…Thus far, the means of attaining such precision medicine-based goals has involved a combination of improved clinical staging; high-resolution imaging techniques; immuno-histochemical-based tumor sub-classification and, increasingly, molecular and pharmacogenomic evaluation to stratify individuals according to inherent risk and likelihood of response to chemotherapeutic regimens [5,[25][26][27][28][29][30][31][32][33][34][35][36][37][38]. The deployment of newer techniques such as liquid biopsies, which quantify circulating tumor DNA, promise to provide additional benefits by allowing serial assessments of response to therapy or the detection of impending recurrence in cases where the tumor has been previously resected or otherwise rendered undetectable by standard methods [39][40][41][42]. Recently a robust dynamic model that allows for the integration of a variety of diverse outcome predictors acquired over time into a single profile and dubbed "Continuous Individualized Risk Index" (CIRI) has been described for patients with breast cancer, chronic lymphocytic leukemia and diffuse large B cell lymphoma.…”

Cell-free nucleic acid patterns in disease prediction and monitoring—hype or hope?

“…Although analysis of solid tumour tissues is a golden standard in oncology [ 117 ], tissue biopsies entail some risks for patients apart from being limited in identifying genetic heterogeneity or tracking neoplasm evolution alternations within a tumour [ 118 ]. Clinical and laboratory advances have broadened tumour-related diagnosis, prognosis and predictive measures.…”