Dysregulated metabolism in EGFR-TKI drug resistant non-small-cell lung cancer: a systematic review
File(s)
Published version
Author(s)
Babuta, Julia
Hall, Zoe
Athersuch, Toby
Type
Journal Article
Abstract
Drug resistance is a common barrier to continued effective treatment in cancer. In non-small-cell lung cancer (NSCLC), tyrosine kinase inhibitors that target the epidermal growth factor receptor (EGFR-TKIs), exhibit good efficacy in cancer treatment until acquired resistance occurs. It has been observed that drug resistance is accompanied by numerous molecular-level changes, including significant shifts in cellular metabolism. The purpose of this study was to critically and systematically review the published literature with respect to how metabolism differs in drug-resistant compared to drug-sensitive NSCLC. Understanding the differences between resistant and sensitive cells is vital and has the potential to allow interventions that enable the re-sensitisation of resistant cells to treatment, and consequently reinitiate the therapeutic effect of EGFR-TKIs. The main literature search was performed using relevant keywords in PubMed and Ovid (Medline) and reviewed using the Covidence platform. Of 1331 potentially relevant literature records retrieved, 27 studies were subsequently selected for comprehensive analysis. Collectively, the literature revealed that NSCLC cell lines resistant to EGFR-TKI treatment possess characteristic metabolic and lipidomic phenotypic signatures that differentiate them from sensitive lines. Further exploration of these reported differences suggests that drug-resistant cell lines are differentially reliant on cellular energy sources and that modulation of relative energy production pathways may lead to the reversal of drug resistance.
Date Issued
2022-07-14
Date Acceptance
2022-07-11
Citation
Metabolites, 2022, 12 (7), pp.1-12
ISSN
2218-1989
Publisher
MDPI AG
Start Page
1
End Page
12
Journal / Book Title
Metabolites
Volume
12
Issue
7
Copyright Statement
© 2022 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)
License URL
Identifier
https://www.mdpi.com/2218-1989/12/7/644
Subjects
EGFR-TKI
NSCLC
drug resistance
lipidomics
metabolism
metabolites
metabolomics
0301 Analytical Chemistry
0601 Biochemistry and Cell Biology
1103 Clinical Sciences
Publication Status
Published
Date Publish Online
2022-07-14