Durable response of lung carcinoma patients to EGFR tyrosine kinase inhibitors is determined by germline polymorphisms in some immune-related genes.
Mol Cancer
; 22(1): 120, 2023 07 29.
Article
em En
| MEDLINE
| ID: mdl-37516818
ABSTRACT
BACKGROUND:
Non-small cell lung cancer is a very poor prognosis disease. Molecular analyses have highlighted several genetic alterations which may be targeted by specific therapies. In clinical practice, progression-free survival on EGFR TKI treatment is between 12 and 14 months. However, some patients progress rapidly in less than 6 months, while others remain free of progression for 16 months or even longer during EGFR TKI treatment.METHODS:
We sequenced tumor exomes from 135 lung cancer patients (79 with EGFR-wildtype (WT), 56 with EGFR-mutant tumors) enrolled in the ALCAPONE trial (genomic analysis of lung cancers by next generation sequencing for personalized treatment).RESULTS:
Some germline polymorphisms were enriched in the EGFR-mutant subset compared to EGFR-WT tumors or to a reference population. However, the most interesting observation was the negative impact of some germline SNPs in immunity-related genes on survival on EGFR TKI treatment. Indeed, the presence of one of three particular SNPs in the HLA-DRB5 gene was associated with a decreased PFS on EGFR TKI. Moreover, some SNPs in the KIR3DL1 and KIR3DL2 genes were linked to a decrease in both progression-free and overall survival of patients with EGFR-mutant tumors.CONCLUSION:
Our data suggest that SNPs in genes expressed by immune cells may influence the response to targeted treatments, such as EGFR TKIs. This indicates that the impact of these cells may not be limited to modulating the response to immunotherapies. Further studies are needed to determine the exact mechanisms underlying this influence and to identify the associated predictive and prognostic markers that would allow to refine treatments and so improve lung cancer patient outcomes. TRIAL REGISTRATION NCT02281214 NGS Genome Analysis in Personalization of Lung Cancer Treatment (ALCAPONE).Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma
/
Carcinoma Pulmonar de Células não Pequenas
/
Neoplasias Pulmonares
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Mol Cancer
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
França