Pancreatic adenocarcinoma: molecular drivers and the role of targeted therapy

Al-Share, Bayan; Hammad, Nour; Diab, Maria

doi:10.1007/s10555-020-09948-w

Cited by 6 publications

(6 citation statements)

References 246 publications

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“…Since this review is focusing on oncogenomic findings in tissue and stool and their clinical significance in the early diagnosis of PC, and to our knowledge transcriptomic analysis has not been done from stool (except of miRNA), gene expression profiling of PC tissue or the functional roles of PC driver genes are not going to be discussed here. However, these topics have recently been reviewed elsewhere [ 31 , 32 , 33 ].…”

Section: Alterations In Tumor Tissuementioning

confidence: 99%

Oncogenomic Changes in Pancreatic Cancer and Their Detection in Stool

et al. 2022

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Pancreatic cancer (PC) is an aggressive malignancy with a dismal prognosis. To improve patient survival, the development of screening methods for early diagnosis is pivotal. Oncogenomic alterations present in tumor tissue are a suitable target for non-invasive screening efforts, as they can be detected in tumor-derived cells, cell-free nucleic acids, and extracellular vesicles, which are present in several body fluids. Since stool is an easily accessible source, which enables convenient and cost-effective sampling, it could be utilized for the screening of these traces. Herein, we explore the various oncogenomic changes that have been detected in PC tissue, such as chromosomal aberrations, mutations in driver genes, epigenetic alterations, and differentially expressed non-coding RNA. In addition, we briefly look into the role of altered gut microbiota in PC and their possible associations with oncogenomic changes. We also review the findings of genomic alterations in stool of PC patients, and the potentials and challenges of their future use for the development of stool screening tools, including the possible combination of genomic and microbiota markers.

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Section: Alterations In Tumor Tissuementioning

confidence: 99%

Oncogenomic Changes in Pancreatic Cancer and Their Detection in Stool

et al. 2022

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“…Despite advances made in the last few decades in understanding PDAC biology and developing new targeted therapies [3][4][5][6], PDAC patients continue to have a dismal prognosis, with a 5-year survival rate of less than 20% [7,8]. Tumor stage is the main prognostic determinant, early-stage tumors being associated with a longer survival than that of locally advanced or metastatic tumors [9].…”

Section: Introductionmentioning

confidence: 99%

Serum miRNA Profiling for Early PDAC Diagnosis and Prognosis: A Retrospective Study

et al. 2021

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Background: Tumor stage predicts pancreatic cancer (PDAC) prognosis, but prolonged and short survivals have been described in patients with early-stage tumors. Circulating microRNA (miRNA) are an emerging class of suitable biomarkers for PDAC prognosis. Our aim was to identify whether serum miRNA signatures predict survival of early-stage PDAC. Methods: Serum RNA from archival 15 stage I-III PDAC patients and 4 controls was used for miRNAs expression profile (Agilent microarrays). PDAC patients with comparable age, gender, diabetes, jaundice and surgery were classified according to survival: less than 14 months (7/15 pts, group A) and more than 22 months (8/15 pts, group B). Bioinformatic data analysis was performed by two-class Significance Analysis of Microarray (SAM) algorithm. Binary logistic regression analyses considering PDAC diagnosis and outcome as dependent variables, and ROC analyses were also performed. Results: 2549 human miRNAs were screened out. At SAM, 76 differentially expressed miRNAs were found among controls and PDAC (FDR = 0.4%), the large majority (50/76, 66%) of them being downregulated in PDAC with respect to controls. Six miRNAs were independently correlated with early PDAC, and among these, hsa-miR-6821-5p was associated with the best ROC curve area in distinguishing controls from early PDAC. Among the 71 miRNAs differentially expressed between groups A and B, the most significant were hsa-miR-3135b expressed in group A only, hsa-miR-6126 and hsa-miR-486-5p expressed in group B only. Eight miRNAs were correlated with the presence of lymph-node metastases; among these, hsa-miR-4669 is of potential interest. hsa-miR-4516, increased in PDAC and found as an independent predictor of survival, has among its putative targets a series of gens involved in key pathways of cancer progression and dissemination, such as Wnt and p53 signalling pathways. Conclusions: A series of serum miRNAs was identified as potentially useful for the early diagnosis of PDAC, and for establishing a prognosis.

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“…The purpose of this review is to highlight recent mechanistic and translational developments that in the opinion of the authors advance our understanding of the complex interplay between KRAS, Yes-Associated Protein (YAP) and Src tyrosine kinase family (SFK) in PDAC development and in designing novel combinatorial therapies. Multiple other therapies for the treatment of PDAC are under development [5], including targeting epigenetic control [6], the extracellular matrix and the immune system [7] but their discussion is beyond the scope of this article.…”

Section: Introductionmentioning

confidence: 99%

Crosstalk between KRAS, SRC and YAP Signaling in Pancreatic Cancer: Interactions Leading to Aggressive Disease and Drug Resistance

Eibl

2021

Cancers

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Pancreatic ductal adenocarcinoma (PDAC), the predominant form of pancreatic cancer, remains a devastating disease. The purpose of this review is to highlight recent literature on mechanistic and translational developments that advance our understanding of a complex crosstalk between KRAS, YAP and Src tyrosine kinase family (SFK) in PDAC development and maintenance. We discuss recent studies indicating the importance of RAS dimerization in signal transduction and new findings showing that the potent pro-oncogenic members of the SFK phosphorylate and inhibit RAS function. These surprising findings imply that RAS may not play a crucial role in maintaining certain subtypes of PDAC. In support of this interpretation, current evidence indicates that the survival of the basal-like subtype of PDAC is less dependent on RAS but relies, at least in part, on the activity of YAP/TAZ. Based on current evidence, we propose that SFK propels PDAC cells to a state of high metastasis, epithelial-mesenchymal transition (EMT) and reduced dependence on KRAS signaling, salient features of the aggressive basal-like/squamous subtype of PDAC. Strategies for PDAC treatment should consider the opposite effects of tyrosine phosphorylation on KRAS and SFK/YAP in the design of drug combinations that target these novel crosstalk mechanisms and overcome drug resistance.

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Pancreatic adenocarcinoma: molecular drivers and the role of targeted therapy

Cited by 6 publications

References 246 publications

Oncogenomic Changes in Pancreatic Cancer and Their Detection in Stool

Oncogenomic Changes in Pancreatic Cancer and Their Detection in Stool

Serum miRNA Profiling for Early PDAC Diagnosis and Prognosis: A Retrospective Study

Crosstalk between KRAS, SRC and YAP Signaling in Pancreatic Cancer: Interactions Leading to Aggressive Disease and Drug Resistance

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