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Alternative Treatment Options to ALK Inhibitor Monotherapy for EML4-ALK-Driven Lung Cancer

Authors :
Savvas Papageorgiou
Sarah L. Pashley
Laura O’Regan
Sam Khan
Richard Bayliss
Andrew M. Fry
Source :
Cancers. 14:3452
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

EML4-ALK is an oncogenic fusion protein that accounts for approximately 5% of NSCLC cases. Targeted inhibitors of ALK are the standard of care treatment, often leading to a good initial response. Sadly, some patients do not respond well, and most will develop resistance over time, emphasizing the need for alternative treatments. This review discusses recent advances in our understanding of the mechanisms behind EML4-ALK-driven NSCLC progression and the opportunities they present for alternative treatment options to ALK inhibitor monotherapy. Targeting ALK-dependent signalling pathways can overcome resistance that has developed due to mutations in the ALK catalytic domain, as well as through activation of bypass mechanisms that utilise the same pathways. We also consider evidence for polytherapy approaches that combine targeted inhibition of these pathways with ALK inhibitors. Lastly, we review combination approaches that use targeted inhibitors of ALK together with chemotherapy, radiotherapy or immunotherapy. Throughout this article, we highlight the importance of alternative breakpoints in the EML4 gene that result in the generation of distinct EML4-ALK variants with different biological and pathological properties and consider monotherapy and polytherapy approaches that may be selective to particular variants.

Subjects

Subjects :
Cancer Research
Oncology

Details

ISSN :
20726694
Volume :
14
Database :
OpenAIRE
Journal :
Cancers
Accession number :
edsair.doi.dedup.....89283c4bf0b41c8279c41feeceb61d6d
Full Text :
https://doi.org/10.3390/cancers14143452