Relevance of neuroendocrine tumours models assessed by kinomic profiling

Although there is evidence of a significant rise of neuroendocrine tumours (NETs) incidence, current treatments are largely insufficient due to somewhat poor knowledge of these tumours. Despite many efforts achieved to expose driver oncogene mutations in NETs, the genetic landscape of NETs is characterized by relatively few mutations and chromosomal aberrations per tumour compared with other tumour types. In addition, NETs display few actionable mutations providing compelling rationale for targeted therapies. Recent works aiming at characterizing currently used NETs in vitro models at the genomic level raised concerns on their reliability as bona fide tools to study NETs biology. However, the lack of actionable mutation in NETs implies that sole use of genomic is not sufficient to describe these models and establish appropriate therapeutic strategies. Several kinases and kinase-involving signalling pathways have been demonstrated as abnormally regulated in NETs. Yet, kinases have only been investigated regardless of their involvement in large intracellular signalling networks. In order to assess the validity of in vitro NETs models to study NETs biology, “next-generation” high throughput functional technologies based on “kinome-wide activity” will demonstrate the similarities between signalling pathways in NETs models and patients’ samples. These approaches will significantly assist in identifying actionable alterations in NETs signalling pathways and guide patient stratification into early-phase clinical trials based on kinase inhibition targeted therapies. Malgré une augmentation significative de l’incidence des tumeurs neuroendocrines (TNE), les traitements actuels sont largement insatisfaisants en raison d’une connaissance insuffisante de ces tumeurs. Malgré les nombreux efforts déployés pour identifier des mutations oncogéniques dans les TNE, le profil génétique des TNE est caractérisé par relativement peu de mutations et aberrations chromosomiques en comparaison avec d’autres types de tumeurs. En outre, les TNE possèdent peu de mutations conductrices justifiant de manière convaincante des stratégies de thérapies ciblées. Des travaux récents visant à caractériser les modèles in vitro de TNE actuellement utilisés au niveau génomique ont émis des doutes quant à leur fiabilité pour étudier la biologie des TNE. Cependant, l’absence de mutation conductrice dans les TNE signifie que la génomique à elle seule ne permet pas de caractériser les modèles d’étude