Year-end Sale % OFF 
Abstract
Pancreatic Ductal Adenocarcinoma (PDAC) is the fourth most common cause of cancer-related death and is the most lethal of common malignancies with a five-year survival rate of <10%. PDAC arises from different types of non-invasive precursor lesions: intraductal papillary mucinous neoplasms, mucinous cystic neoplasms and pancreatic intraepithelial neoplasia. The genetic landscape of PDAC is characterized by the presence of four frequently-mutated genes: KRAS, CDKN2A, TP53 and SMAD4. The development of mouse models of PDAC has greatly contributed to the understanding of the molecular and cellular mechanisms through which driver genes contribute to pancreatic cancer development. Particularly, oncogenic KRAS-driven genetically-engineered mouse models that phenotypically and genetically recapitulate human pancreatic cancer have clarified the mechanisms through which various mutated genes act in neoplasia induction and progression and have led to identifying the possible cellular origin of these neoplasias. Patient-derived xenografts are increasingly used for preclinical studies and for the development of personalized medicine strategies. The studies of the purification and characterization of pancreatic cancer stem cells have suggested that a minority cell population is responsible for initiation and maintenance of pancreatic adenocarcinomas. The study of these cells could contribute to the identification and clinical development of more efficacious drug treatments.
Highlights
The pancreas possesses two functional cellular compartments, endocrine and exocrine
This study provided a characterization of the rare cases of Pancreatic Ductal Adenocarcinoma (PDAC) KRAS wild-type (7% of total); these tumors displayed mutations in other drivers, such as GNAS, JAK1, CTNNB1, BRAF and showed significantly elevated TSC/MTOR signaling activity, compared to the KRAS-mutant tumors [21]
A recent study reported the molecular characterization of a large set of intraductal papillary mucinous neoplasms (IPMNs) showing that 91% of these tumors display KRAS or GNAS mutations and 47% had mutations of both genes; mutations of RNF43 are observed in 38% of cases; CDKN2A (3%), CTNNB1 (6%), SMAD4 (5%), TP53 (9%) mutations are rare; copy number alteration events are less frequent and involve genes such as RNF43 (11%), SMAD4 (10%), CDKN2A (8%), VHL (4%); aneuploidy was observed in 50% of samples [30]
Summary
The pancreas possesses two functional cellular compartments, endocrine and exocrine. The exocrine pancreas comprises acinar, ductal and centroacinar cells. These authors have explored PanINs and IPMNs in patients with a family history of pancreatic cancer [25] The results of this interesting study showed that more than 80% of PanIN and IPMN lesions do not have common somatic copy number gene alterations; in contrast, about 95% of PanINs and IPMNs harbor mutations in KRAS [25]. A recent study reported the molecular characterization of a large set of IPMNs showing that 91% of these tumors display KRAS or GNAS mutations and 47% had mutations of both genes; mutations of RNF43 are observed in 38% of cases; CDKN2A (3%), CTNNB1 (6%), SMAD4 (5%), TP53 (9%) mutations are rare; copy number alteration events are less frequent and involve genes such as RNF43 (11%), SMAD4 (10%), CDKN2A (8%), VHL (4%); aneuploidy was observed in 50% of samples [30]. NThAesmfroumtatneodrUmPaFl R1 NobAsse.rTvhede minuAtaStCedP UisPdFe1feocbtsiveervienditisnfAunSCctPioins,daenfdecatibvneoirnmitaslfRuNncAtiotrna,nasncdriapbtsno(ir.me.,aTl PR5N3Agetrnaentsrcarnipsctsri(pi.tes.), TwPe5r3e goebnsertvreadnsicnritphtess)ewtuemreoorbss[e5r5v]e. d in these tumors [55]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
