Liquid biopsy: a step forward towards precision medicine in urologic malignancies

Abstract

There is a growing trend towards exploring the use of a minimally invasive "liquid biopsy" to identify biomarkers in a number of cancers, including urologic malignancies. Multiple aspects can be assessed in circulating cell-free DNA, including cell-free DNA levels, integrity, methylation and mutations. Other prospective liquid biopsy markers include circulating tumor cells, circulating RNAs (miRNA, lncRNAs and mRNAs), cell-free proteins, peptides and exosomes have also emerged as non-invasive cancer biomarkers. These circulating molecules can be detected in various biological fluids, including blood, urine, saliva and seminal plasma. Liquid biopsies hold great promise for personalized medicine due to their ability to provide multiple non-invasive global snapshots of the primary and metastatic tumors. Molecular profiling of circulating molecules has been a stepping-stone to the successful introduction of several non-invasive multi-marker tests into the clinic. In this review, we provide an overview of the current state of cell-free DNA-based kidney, prostate and bladder cancer biomarker research and discuss the potential utility other circulating molecules. We will also discuss the challenges and limitations facing non-invasive cancer biomarker discovery and the benefits of this growing area of translational research.

Keywords: Biomarkers; Bladder cancer; Cancer treatment; Cell-free DNA; Circulating tumor DNA; Circulating tumor cells; Exosomse; Kidney cancer; Liquid biopsy; Long non-coding RNA; Personalized medicine; Precision medicine; Predictive markers; Prostate cancer; Tumor markers; miRNAs.

Fig. 1

Circulating molecules in liquid biopsy. There are a number of molecules that can be measured in body fluids including cell-free DNA, circulating tumor cells (CTCs), different circulating RNA classes (miRNAs, lncRNAs, mRNAs), cell-free proteins and exosomes. Cell-free DNA escapes into circulation from the primary tumor or metastatic loci through necrosis or apoptosis of tumor cells. Circulating cell-free DNA can then be used as a liquid biopsy to measure DNA levels, integrity, methylation, mutational status and copy number aberration

Fig. 2

Circulating molecules can be detected in various biological fluids. Circulating molecules are present in a number of biological fluids, including urine, serum, plasma, cerebrospinal fluid, seminal plasma and saliva. These can be obtained using a liquid biopsy