Deconstructing Pancreatic Cancer Using Next Generation-Omic Technologies–From Discovery to Knowledge-Guided Platforms for Better Patient Management

Schreyer, Daniel; Neoptolemos, John P.; Barry, Simon T.; Bailey, Peter J.

doi:10.3389/fcell.2021.795735

Cited by 12 publications

(3 citation statements)

References 149 publications

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“…In addition, a few cases have immune checkpoint proteins up-regulation suggesting that they belong to the immunogenic subtype. Genomic classifications have yet to be validated as predictive markers of therapies and their clinical value remains to be determined (66). However, they may imply different pathogenesis of sub-types, which could facilitate successful rational targeted therapies development.…”

Section: Discussionmentioning

confidence: 99%

Pancreatic adenocarcinomas without KRAS, TP53, CDKN2A and SMAD4 mutations and CDKN2A/CDKN2B copy number alterations: a review of the genomic landscape to unveil therapeutic avenues

Voutsadakis¹,

Digklia²

2023

Chin Clin Oncol

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Background: Pancreatic adenocarcinoma is one of the cancers with the worst prognosis. The current treatment paradigm based on combination chemotherapy has improved survival over the last decade, but the disease is still fatal in most cases. New therapies exploiting the increasing understanding of the molecular pathology of the disease are needed. Although the disease presents with few recurrent molecular alterations, these represent opportunities for targeted treatments to be developed. However, a minority of cases are devoid of these common alterations. A description of the molecular landscape of this sub-set of pancreatic adenocarcinoma could uncover other molecular lesions present in them that could serve as therapeutic targets.Methods: The sub-set of pancreatic cancers without the common alterations in KRAS, TP53, CDKN2A and SMAD4 has been examined from published and publicly available pancreatic cancer cohorts for determination of their clinical and molecular characteristics. The cBioportal platform was used for this evaluation and the OncoKB knowledgebase was used for determination of the functional significance of discovered mutations.Results: About 5% to 10% of pancreatic adenocarcinomas present without the usual molecular alterations that characterize the disease. These cases tend to be genomically stable and have low prevalence of microsatellite or chromosome instability. Molecular alterations that are observed in pancreatic cancers in lower frequencies than the four most prevalent alterations, such as DNA Damage Response and epigenetic modifier mutations, are still observed in the sub-set without the common alterations and may be pathogenically relevant.Conclusions: Despite the absence of most frequent pancreatic cancer alterations in a sub-set of pancreatic adenocarcinomas, this sub-set possesses other alterations in frequencies similar to the rest of pancreatic cancers. Putative targeting of alterations present is discussed and can serve as the basis for targeted therapies development.

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Section: Discussionmentioning

confidence: 99%

Pancreatic adenocarcinomas without KRAS, TP53, CDKN2A and SMAD4 mutations and CDKN2A/CDKN2B copy number alterations: a review of the genomic landscape to unveil therapeutic avenues

Voutsadakis¹,

Digklia²

2023

Chin Clin Oncol

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“…Gene expression may confirm morphological heterogeneity 54 or identify heterogeneity in the absence of morphological changes 51,55 . Spatial transcriptomics can identify subpopulations with gene expression patterns associated with prognosis or response to targeted treatments such as mRNA fusion transcripts, 56 gene expression patterns associated with chemotherapy response 57 and treatment‐resistant subpopulations. The presence of tumour heterogeneity, including of the tumour microenvironment, is associated with poorer clinical outcomes in several cancer types 10,51 .…”

Section: Potential Uses Of Spatial Transcriptomics In Anatomical Path...mentioning

confidence: 99%

Spatial transcriptomics and the anatomical pathologist: Molecular meets morphology

Pang,

Byrne,

Bergin

et al. 2023

Histopathology

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In recent years anatomical pathology has been revolutionised by the incorporation of molecular findings into routine diagnostic practice, and in some diseases the presence of specific molecular alterations are now essential for diagnosis. Spatial transcriptomics describes a group of technologies that provide up to transcriptome‐wide expression profiling while preserving the spatial origin of the data, with many of these technologies able to provide these data using a single tissue section. Spatial transcriptomics allows expression profiling of highly specific areas within a tissue section potentially to subcellular resolution, and allows correlation of expression data with morphology, tissue type and location relative to other structures. While largely still research laboratory‐based, several spatial transcriptomics methods have now achieved compatibility with formalin‐fixed paraffin‐embedded tissue (FFPE), allowing their use in diagnostic tissue samples, and with further development potentially leading to their incorporation in routine anatomical pathology practice. This mini review provides an overview of spatial transcriptomics methods, with an emphasis on platforms compatible with FFPE tissue, approaches to assess the data and potential applications in anatomical pathology practice.

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“…Improvements in the cost and speed of next-generation sequencing have allowed for the expansion of multiomic datasets in pancreatic cancer research ( 7 ). As a result, these data have facilitated the implementation of precision medicine.…”

Section: Improving Diversity In Precision Medicinementioning

confidence: 99%

From bench to bedside: Pursuing equity in precision medicine approaches to pancreatic cancer care

Herremans

Riner²,

Charles³

et al. 2022

Front. Oncol.

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Deconstructing Pancreatic Cancer Using Next Generation-Omic Technologies–From Discovery to Knowledge-Guided Platforms for Better Patient Management

Cited by 12 publications

References 149 publications

Pancreatic adenocarcinomas without KRAS, TP53, CDKN2A and SMAD4 mutations and CDKN2A/CDKN2B copy number alterations: a review of the genomic landscape to unveil therapeutic avenues

Pancreatic adenocarcinomas without KRAS, TP53, CDKN2A and SMAD4 mutations and CDKN2A/CDKN2B copy number alterations: a review of the genomic landscape to unveil therapeutic avenues

Spatial transcriptomics and the anatomical pathologist: Molecular meets morphology

From bench to bedside: Pursuing equity in precision medicine approaches to pancreatic cancer care

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