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Role of oncogenic KRAS in the diagnosis, prognosis and treatment of pancreatic cancer

Nature reviews. Gastroenterology & hepatology, 2020-03, Vol.17 (3), p.153-168 [Peer Reviewed Journal]

COPYRIGHT 2020 Nature Publishing Group ;2020© Springer Nature Limited 2020 ;Springer Nature Limited 2020. ;ISSN: 1759-5045 ;EISSN: 1759-5053 ;DOI: 10.1038/s41575-019-0245-4 ;PMID: 32005945

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Title:
Role of oncogenic KRAS in the diagnosis, prognosis and treatment of pancreatic cancer
Author: Buscail, Louis ; Bournet, Barbara ; Cordelier, Pierre
Subjects: Adenocarcinoma ; Animals ; Biomarkers, Tumor - genetics ; Carcinoma, Pancreatic Ductal - diagnosis ; Carcinoma, Pancreatic Ductal - genetics ; Carcinoma, Pancreatic Ductal - therapy ; Care and treatment ; Cell migration ; Cell proliferation ; Cell survival ; Cytopathology ; Diagnosis ; Disease Models, Animal ; Gene expression ; Gene mutations ; Genetic aspects ; Health aspects ; Humans ; Identification and classification ; Intracellular signalling ; K-Ras protein ; Medical prognosis ; Mice, Transgenic ; Mutation ; Nucleotides ; Oncogenes ; Pancreatic cancer ; Pancreatic Neoplasms - diagnosis ; Pancreatic Neoplasms - genetics ; Pancreatic Neoplasms - therapy ; Pharmacokinetics ; Post-translation ; Prognosis ; Proto-Oncogene Proteins p21(ras) - genetics ; Proto-Oncogene Proteins p21(ras) - physiology ; Signal transduction ; Signal Transduction - genetics ; Toxicity testing ; Transcription factors
Is Part Of: Nature reviews. Gastroenterology & hepatology, 2020-03, Vol.17 (3), p.153-168
Description: Pancreatic ductal adenocarcinoma (PDAC) is predicted to be the second most common cause of death within the next 10 years. The prognosis for this disease is poor despite diagnostic progress and new chemotherapeutic regimens. The oncogenic KRAS mutation is the major event in pancreatic cancer; it confers permanent activation of the KRAS protein, which acts as a molecular switch to activate various intracellular signalling pathways and transcription factors inducing cell proliferation, migration, transformation and survival. Several laboratory methods have been developed to detect KRAS mutations in biological samples, including digital droplet PCR (which displays high sensitivity). Clinical studies have revealed that a KRAS mutation assay in fine-needle aspiration material combined with cytopathology increases the sensitivity, accuracy and negative predictive value of cytopathology for a positive diagnosis of pancreatic cancer. In addition, the presence of KRAS mutations in serum and plasma (liquid biopsies) correlates with a worse prognosis. The presence of mutated KRAS can also have therapeutic implications, whether at the gene level per se, during its post-translational maturation, interaction with nucleotides and after activation of the various oncogenic signals. Further pharmacokinetic and toxicological studies on new molecules are required, especially small synthetic molecules, before they can be used in the therapeutic arsenal for pancreatic ductal adenocarcinoma.
Publisher: England: Nature Publishing Group
Language: English
Identifier: ISSN: 1759-5045
EISSN: 1759-5053
DOI: 10.1038/s41575-019-0245-4
PMID: 32005945
Source: MEDLINE
ProQuest Central

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Role of oncogenic KRAS in the diagnosis, prognosis and treatment of pancreatic cancer

COPYRIGHT 2020 Nature Publishing Group ;2020© Springer Nature Limited 2020 ;Springer Nature Limited 2020. ;ISSN: 1759-5045 ;EISSN: 1759-5053 ;DOI: 10.1038/s41575-019-0245-4 ;PMID: 32005945

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