Liquid Biopsy - the Future for Cancer Diagnostics?

Needle aspirates and tissue biopsies are commonplace in veterinary medicine but are not without their drawbacks for tumor diagnosis. Here Matthew Breen and Claire Wiley describe a new technique for the early diagnosis of canine bladder cancer, and discuss what the future may hold for liquid biopsy procedures.

Matthew Breen
PhD, C.Biol, FRSB
 

Claire Wiley
VMD, Dipl. ACVIM (SAIM)
 

Introduction

For many cancers, histopathologic evaluation of a biopsy of a suspicious mass has been the gold standard for diagnosis for many years. However, the biopsy process itself may be invasive, costly, and can be associated with complications to the patient. For some cancers, obtaining a solid biopsy may also increase the risk of disseminating tumor cells, leading to added concerns. In a clinical setting, identifying the presence of a specific tumor in a patient can be challenging. To complement conventional invasive procedures, clinicians have been eager to identify less invasive, safer, and more affordable alternatives to obtaining materials suitable for diagnostic evaluation. The term “cancer signature” is employed to describe an indicator of the presence of a tumor; methods to detect such a “signature” are being urgently sought, ideally with high sensitivity and specificity. Liquid biopsy embodies these desirable characteristics by offering a non-invasive method for detecting genetic alterations in tumors through analysis of tumor cells and tumor-derived cell-free DNA (cfDNA) in plasma and urine. This approach provides opportunities for improving cancer detection and identification, and also for monitoring the impact of therapy on patients over time. Advancing quickly in human medicine, liquid biopsy is being incorporated into numerous drug development programs, and is likely to be rapidly integrated into clinical care for human patients.

What is liquid biopsy?

Tumors release cells and DNA into surrounding tissues and fluids, thus offering the opportunity to assess the genetic composition of a solid tumor from sampling body fluids. Use of such fluids is referred to as a “liquid biopsy” (1). Although the presence of circulating cell-free nucleic acids (cfNAs) was first described almost 70 years ago, the significance was not recognized until 1994, when fragments of a driver oncogene (a mutant RAS gene) were identified in the blood of cancer patients (1).

It is now recognized that circulating cell-free tumor DNA concentrations are higher in cancer patients than in normal controls, and that the presence of metastases is generally associated with even higher levels (2). The mechanism for release of nucleic acids into surrounding tissues is hypothesized to be associated with the fast turnover of cells and resulting apoptosis (1). Traditionally, the term “liquid biopsy” was regarded as referring to the identification of neoplastic biological materials (e.g., circulating tumor cells or cfDNA) in the peripheral bloodstream (3). More recently, the definition has broadened to encompass all body fluids, including urine, cerebrospinal fluid (CSF), cavitary effusions, etc. (3). [...]