KRAS wild-type pancreatic ductal adenocarcinoma: molecular pathology and therapeutic opportunities.
BRAF
KRAS
MSI
dMMR
fusion genes
pancreatic cancer
Journal
Journal of experimental & clinical cancer research : CR
ISSN: 1756-9966
Titre abrégé: J Exp Clin Cancer Res
Pays: England
ID NLM: 8308647
Informations de publication
Date de publication:
28 Oct 2020
28 Oct 2020
Historique:
received:
16
05
2020
accepted:
13
10
2020
entrez:
29
10
2020
pubmed:
30
10
2020
medline:
7
7
2021
Statut:
epublish
Résumé
Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease, whose main molecular trait is the MAPK pathway activation due to KRAS mutation, which is present in 90% of cases.The genetic landscape of KRAS wild type PDAC can be divided into three categories. The first is represented by tumors with an activated MAPK pathway due to BRAF mutation that occur in up to 4% of cases. The second includes tumors with microsatellite instability (MSI) due to defective DNA mismatch repair (dMMR), which occurs in about 2% of cases, also featuring a high tumor mutational burden. The third category is represented by tumors with kinase fusion genes, which marks about 4% of cases. While therapeutic molecular targeting of KRAS is an unresolved challenge, KRAS-wild type PDACs have potential options for tailored treatments, including BRAF antagonists and MAPK inhibitors for the first group, immunotherapy with anti-PD-1/PD-L1 agents for the MSI/dMMR group, and kinase inhibitors for the third group.This calls for a complementation of the histological diagnosis of PDAC with a routine determination of KRAS followed by a comprehensive molecular profiling of KRAS-negative cases.
Identifiants
pubmed: 33115526
doi: 10.1186/s13046-020-01732-6
pii: 10.1186/s13046-020-01732-6
pmc: PMC7594413
doi:
Substances chimiques
Antineoplastic Agents
0
KRAS protein, human
0
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
227Subventions
Organisme : Associazione Italiana per la Ricerca sul Cancro
ID : 12182
Organisme : Fondazione Cariverona: Oncology Biobank Project "Antonio Schiavi"
ID : 203885/2017
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