Integration of liquid biopsy and pharmacogenomics for precision therapy of EGFR mutant and resistant lung cancers

The advent of molecular profiling has revolutionized the treatment of lung cancer by comprehensively delineating the genomic landscape of the epidermal growth factor receptor (EGFR) gene. Drug resistance caused by EGFR mutations and genetic polymorphisms of drug metabolizing enzymes and transporters impedes effective treatment of EGFR mutant and resistant lung cancer. This review appraises current literature, opportunities, and challenges associated with liquid biopsy and pharmacogenomic (PGx) testing as precision therapy tools in the management of EGFR mutant and resistant lung cancers. Liquid biopsy could play a potential role in selection of precise tyrosine kinase inhibitor (TKI) therapies during different phases of lung cancer treatment. This selection will be based on the driver EGFR mutational status, as well as monitoring the development of potential EGFR mutations arising during or after TKIs treatment, since some of these new mutations may be druggable targets for alternative TKIs. Several studies have identified the utility of liquid biopsy in the identification of EGFR driver and acquired resistance with good sensitivities for various blood-based biomarkers. With a plethora of sequencing technologies and platforms available currently, further evaluations using randomized controlled trials (RCTs) in multicentric, multiethnic and larger patient cohorts could enable optimization of liquid-based assays for the detection of EGFR mutations, and support testing of CYP450 enzymes and drug transporter polymorphisms to guide precise dosing of EGFR TKIs.