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David S. Ettinger, MD, FACP, FCCP


Use of Liquid Biopsies in Managing EGFR-Mutant and Resistant Lung Cancers

By: Victoria Kuhr, BA
Posted: Monday, August 1, 2022

According to Mahadev Rao, PhD, of Manipal Academy of Higher Education, Manipal, Karnataka, India, and colleagues, liquid biopsies represent an alternative and complementary tool to tissue biopsies for lung cancer screening, particularly regarding targeted therapies for EGFR-mutant and resistant lung cancers. However, liquid biopsies have limitations to screening that need to be addressed before clinical use on a global scale. These review findings were published in Molecular Cancer.

“Employing liquid biopsy for serial molecular profiling of EGFR-mutant and resistant lung cancer patients at an individual level as well as at population subsets could represent a potential precise screening and monitoring tool by identifying precise doses of tyrosine kinase inhibitors against targetable EGFR mutations,” said the study authors.

Several studies have found promising results in using liquid biopsies to identify the EGFR gene. Liquid biopsies help monitor EGFR-acquired resistance to tyrosine kinase inhibitor treatment in real time through various blood-based markers.

In these studies, patients with the EGFR mutations responded well to EGFR tyrosine kinase inhibitor treatment. These patients saw improved progression-free survival, overall response rate, and response to treatment. However, these treatments decreased in effectiveness as lung cancer progressed and acquired resistance to treatment increased.

Liquid biopsy–based detection can detect only about half of the resistance mechanisms in patients with non–small cell lung cancer who developed acquired resistance to first- or second-generation tyrosine kinase inhibitors. Some liquid biopsy assays have a lower sensitivity for EGFR mutations compared with tissue biopsy. This lower detection level may be attributed to sampling from different tumor cell populations as well as differing sequencing technologies. Liquid biopsies have less accuracy in early screening of lung cancer compared with tissue biopsy due to low copy numbers in peripheral blood. Additionally, guidelines or harmonization with different sampling technologies to support liquid biopsy is lacking.

Disclosure: The study authors reported no conflicts of interest.

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