A Closer Look at EGFR Inhibitor Resistance in Non-Small Cell Lung Cancer through the Lens of Precision Medicine.
EGFR
drug resistance
epigenetics
genetic/nongenetic
non-small cell lung cancer
Journal
Journal of clinical medicine
ISSN: 2077-0383
Titre abrégé: J Clin Med
Pays: Switzerland
ID NLM: 101606588
Informations de publication
Date de publication:
01 Mar 2023
01 Mar 2023
Historique:
received:
25
01
2023
revised:
22
02
2023
accepted:
26
02
2023
entrez:
11
3
2023
pubmed:
12
3
2023
medline:
12
3
2023
Statut:
epublish
Résumé
The development of EGFR small-molecule inhibitors has provided significant benefit for the affected patient population. Unfortunately, current inhibitors are no curative therapy, and their development has been driven by on-target mutations that interfere with binding and thus inhibitory activity. Genomic studies have revealed that, in addition to these on-target mutations, there are also multiple off-target mechanisms of EGFR inhibitor resistance and novel therapeutics that can overcome these challenges are sought. Resistance to competitive 1st-generation and covalent 2nd- and 3rd-generation EGFR inhibitors is overall more complex than initially thought, and novel 4th-generation allosteric inhibitors are expected to suffer from a similar fate. Additional nongenetic mechanisms of resistance are significant and can include up to 50% of the escape pathways. These potential targets have gained recent interest and are usually not part of cancer panels that look for alterations in resistant patient specimen. We discuss the duality between genetic and nongenetic EGFR inhibitor drug resistance and summarize current team medicine approaches, wherein clinical developments, hand in hand with drug development research, drive potential opportunities for combination therapy.
Identifiants
pubmed: 36902723
pii: jcm12051936
doi: 10.3390/jcm12051936
pmc: PMC10003860
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
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