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

Jill Kolesar; Spencer Peh; Levin Thomas; Gayathri Baburaj; Nayonika Mukherjee; Raveena Kantamneni; Shirley Lewis; Ananth Pai; Karthik S Udupa; Naveena Kumar An; Vivek M Rangnekar; Mahadev Rao

doi:10.1186/s12943-022-01534-8

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

Journal article

Open access

Peer reviewed

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

Jill Kolesar, Spencer Peh, Levin Thomas, Gayathri Baburaj, Nayonika Mukherjee, Raveena Kantamneni, Shirley Lewis, Ananth Pai, Karthik S Udupa, Naveena Kumar An, …

Molecular cancer, Vol.21(1), 61

02/24/2022

DOI: 10.1186/s12943-022-01534-8

PMCID: PMC8867675

PMID: 35209919

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Abstract

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.

Mutation

Pharmacogenetics

Drug Resistance, Neoplasm

ErbB Receptors - genetics

ErbB Receptors - metabolism

Humans

Liquid Biopsy

Lung Neoplasms - drug therapy

Lung Neoplasms - genetics

Lung Neoplasms - pathology

Precision Medicine

Protein Kinase Inhibitors - pharmacology

Protein Kinase Inhibitors - therapeutic use

Randomized Controlled Trials as Topic

Details

Title: Subtitle: Integration of liquid biopsy and pharmacogenomics for precision therapy of EGFR mutant and resistant lung cancers
Creators: Jill Kolesar - University of Kentucky
Spencer Peh - University of Kentucky
Levin Thomas - Manipal Academy of Higher Education
Gayathri Baburaj - Manipal Academy of Higher Education
Nayonika Mukherjee - Manipal Academy of Higher Education
Raveena Kantamneni - Manipal Academy of Higher Education
Shirley Lewis - Manipal Academy of Higher Education
Ananth Pai - Manipal Academy of Higher Education
Karthik S Udupa - Manipal Academy of Higher Education
Naveena Kumar An - Kasturba Medical College, Manipal
Vivek M Rangnekar - University of Kentucky
Mahadev Rao - Manipal Academy of Higher Education
Resource Type: Journal article
Publication Details: Molecular cancer, Vol.21(1), 61
DOI: 10.1186/s12943-022-01534-8
PMID: 35209919
PMCID: PMC8867675
NLM abbreviation: Mol Cancer
ISSN: 1476-4598
eISSN: 1476-4598
Language: English
Date published: 02/24/2022
Academic Unit: Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
Record Identifier: 9984696544402771

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