Mechanisms of Acquired Resistance and Tolerance to EGFR Targeted Therapy in Non-Small Cell Lung Cancer

Non-small cell lung cancers (NSCLC) harboring activating mutations of the epidermal growth factor receptor (EGFR) are treated with specific tyrosine kinase inhibitors (EGFR-TKIs) of this receptor, resulting in clinically responses that can generally last several months. Unfortunately, EGFR-targeted...

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Bibliographic Details
Published in:Cancers Vol. 15; no. 2; p. 504
Main Authors: Chhouri, Houssein, Alexandre, David, Grumolato, Luca
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 13.01.2023
MDPI
Subjects:
Animals
Antitumor agents
Cancer therapies
Carcinoma, Non-Small-Cell Lung
Chemotherapy
Clinical trials
Drug tolerance
Epidermal growth factor
Epidermal growth factor receptors
Exons
Growth factors
Hepatocyte Growth Factor
Humans
Kinases
Life Sciences
Ligands
Lung cancer
Lung Neoplasms
Metastasis
Mice
Mutation
Non-small cell lung carcinoma
Protein Kinase Inhibitors
Protein-tyrosine kinase
Proto-Oncogene Proteins c-met
Response rates
Review
Small cell lung carcinoma
Tumors
non-small cell lung cancer
targeted therapy
EGFR-TKI
drug resistance
drug tolerant persister cells
cellular barcoding
lung cancer
preclinical models
targeted therapies
transcriptomic
hepatocyte growth factor
tyrosine kinase receptor
ISSN:2072-6694, 2072-6694
Online Access:Get full text
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Description
Summary:Non-small cell lung cancers (NSCLC) harboring activating mutations of the epidermal growth factor receptor (EGFR) are treated with specific tyrosine kinase inhibitors (EGFR-TKIs) of this receptor, resulting in clinically responses that can generally last several months. Unfortunately, EGFR-targeted therapy also favors the emergence of drug tolerant or resistant cells, ultimately resulting in tumor relapse. Recently, cellular barcoding strategies have arisen as a powerful tool to investigate the clonal evolution of these subpopulations in response to anti-cancer drugs. In this review, we provide an overview of the currently available treatment options for NSCLC, focusing on EGFR targeted therapy, and discuss the common mechanisms of resistance to EGFR-TKIs. We also review the characteristics of drug-tolerant persister (DTP) cells and the mechanistic basis of drug tolerance in EGFR-mutant NSCLC. Lastly, we address how cellular barcoding can be applied to investigate the response and the behavior of DTP cells upon EGFR-TKI treatment.
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PMCID: PMC9856371
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers15020504