What is liquid biopsy?

The need for a correct identification of all patients presenting an EGFR gene mutation in recent years, even when the sample contained a low percentage of neoplastic cells, paved the way for alternative methods to analyze tissue samples. In fact, it is not always possible to perform a biopsy or obtain an appropriate cytological sample for molecular analysis.

Blood is thus an important resource that allows one to obtain information about molecular alterations for prognostic and predictive therapy response purposes. Over the years, studies have been conducted to isolate circulating tumor cells or free circulating DNA in order to analyze the proportion of circulating tumor DNA and perform molecular analyses on a simple blood sample. It is believed that the circulating tumor DNA derives for the most part from necrotic or apoptotic tumor cells.

Several national and international groups have developed methods to search for EGFR gene mutations or EML4-ALK gene translocations on blood. These cases are referred to as liquid biopsies, as the genetic analysis is conducted on the plasma.

Tumor marker test

In 2014, the EMA approved the use of plasma to evaluate EGFR mutational status for patients who are candidates for treatment with tyrosine kinase inhibitors of EGFR. With the development of osimertinib, the liquid biopsy is mainly used to identify the T790M mutation of EGFR gene in patients on first- and second-generation EGFR inhibitors with tumor progression.

However, there are differences in terms of sensitivity and specificity when the analysis is performed on plasma with respect to tissue. Therefore, further refinements of the methods in use today are necessary to make liquid biopsy a routine practice.

FoundationOne®Liquid, using a single blood sample, can analyze 70 tumor-related genes to detect the main genomic alteration classes and identify the presence of high microsatellite instability, a parameter used to predict a patient’s response to immunotherapy.

How to make a liquid biopsy

A liquid biopsy is performed using a simple blood sample that is analyzed to identify molecular markers. It is a much less invasive procedure than the ‘traditional’ biopsy.