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KRAS wild-type pancreatic ductal adenocarcinoma: molecular pathology and therapeutic opportunities.
- Source :
-
Journal of experimental & clinical cancer research : CR [J Exp Clin Cancer Res] 2020 Oct 28; Vol. 39 (1), pp. 227. Date of Electronic Publication: 2020 Oct 28. - Publication Year :
- 2020
-
Abstract
- 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.
- Subjects :
- Carcinoma, Pancreatic Ductal genetics
Carcinoma, Pancreatic Ductal pathology
Humans
Pancreatic Neoplasms genetics
Pancreatic Neoplasms pathology
Pancreatic Neoplasms
Antineoplastic Agents therapeutic use
Carcinoma, Pancreatic Ductal drug therapy
Molecular Targeted Therapy
Mutation
Pancreatic Neoplasms drug therapy
Pathology, Molecular
Proto-Oncogene Proteins p21(ras) genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1756-9966
- Volume :
- 39
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of experimental & clinical cancer research : CR
- Publication Type :
- Academic Journal
- Accession number :
- 33115526
- Full Text :
- https://doi.org/10.1186/s13046-020-01732-6