SNFGE SNFGE
 
Thématique :
- Cancers autres (hors CCR et CHC)
Originalité :
Très original
Solidité :
A confirmer
Doit faire évoluer notre pratique :
Dans certains cas
 
 
Nom du veilleur :
Professeur Thomas APARICIO
Coup de coeur :
 
 
Gut
  2018/09  
 
  2018 Sep. pii: gutjnl-2018-316522.  
  doi: 10.1136/gutjnl-2018-316522.  
 
  Liquid biopsies to track trastuzumab resistance in metastatic HER2-positive gastric cancer.  
 
  Wang DS, Liu ZX, Lu YX, Bao H, Wu X, Zeng ZL, Liu Z, Zhao Q, He CY, Lu JH, Wang ZQ, Qiu MZ, Wang F, Wang FH, Li YH, Wang XN, Xie D, Jia WH, Shao YW, Xu RH  
  https://www.ncbi.nlm.nih.gov/pubmed/30269082  
 
 

Abstract
 

OBJECTIVE:

To monitor trastuzumab resistance and determine the underlying mechanisms for the limited response rate and rapid emergence of resistance of HER2+ metastatic gastric cancer (mGC).

DESIGN:

Targeted sequencing of 416 clinically relevant genes was performed in 78 paired plasma and tissue biopsy samples to determine plasma-tissue concordance. Then, we performed longitudinal analyses of 97 serial plasma samples collected from 24 patients who were HER2+  to track the resistance during trastuzumab treatment and validated the identified candidate resistance genes.

RESULTS:

The results from targeted sequencing-based detection of somatic copy number alterations (SCNA) of HER2 gene were highly consistent with fluorescence in situ hybridisation data, and the detected HER2 SCNA was better than plasma carcinoembryonic antigen levels at predicting tumour shrinkage and progression. Furthermore, most patients with innate trastuzumab resistance presented high HER2SCNA during progression compared with baseline, while HER2 SCNA decreased in patients with acquired resistance. PIK3CA mutations were significantly enriched in patients with innate resistance, and ERBB2/4 genes were the most mutated genes, accounting for trastuzumab resistance in six (35.3%) and five (29.4%) patients in baseline and progression plasma, respectively. Patients with PIK3CA/R1/C3 or ERBB2/4 mutations in the baseline plasma had significantly worse progression-free survival. Additionally, mutations in NF1 contributed to trastuzumab resistance, which was further confirmed through in vitro and in vivo studies, while combined HER2 and MEK/ERK blockade overcame trastuzumab resistance.

CONCLUSION:

Longitudinal circulating tumour DNA sequencing provides novel insights into gene alterations underlying trastuzumab resistance in HER2+mGC.

 
Question posée
 
L’analyse de l’ADN circulant peut-elle prédire l’efficacité d’un traitement par trastuzumab chez des patients atteints d’un adénocarcinome gastrique métastatique HER2+ ?
 
Question posée
 
Oui.
 
Commentaires

Résultats très intéressants obtenus sur un échantillon de faible puissance. A confirmer sur une plus grande série non asiatique.

 
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